The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index; 4 of the 24 sources its claims cite were checked for support.
Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study
Open accessAbstract
Whole-genome sequencing (WGS) brings comprehensive insights to cancer genome interpretation. To explore the clinical value of WGS, we sequenced 254 triple-negative breast cancers (TNBCs) for which associated treatment and outcome data were collected between 2010 and 2015 via the population-based Sweden Cancerome Analysis Network-Breast (SCAN-B) project (ClinicalTrials.gov ID:NCT02306096). Applying the HRDetect mutational-signature-based algorithm to classify tumors, 59% were predicted to have homologous-recombination-repair deficiency (HRDetect-high): 67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2. A novel mechanism of BRCA1 abrogation was discovered via germline SINE-VNTR-Alu retrotransposition. HRDetect provided independent prognostic information, with HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (hazard ratio (HR) = 0.42; 95% confidence interval (CI) = 0.2-0.87) and distant relapse-free interval (HR = 0.31, CI = 0.13-0.76) compared to HRDetect-low, regardless of whether a genetic/epigenetic cause was identified. HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had the poorest outcomes. HRDetect-low cancers also had inadequate outcomes: ~4.7% were mismatch-repair-deficient (another targetable defect, not typically sought) and they were enriched for (but not restricted to) PIK3CA/AKT1 pathway abnormalities. New treatment options need to be considered for now-discernible HRDetect-intermediate and HRDetect-low categories. This population-based study advocates for WGS of TNBC to better inform trial stratification and improve clinical decision-making.
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56 Own result · 22 Own interpretation · 14 Not checked yet · 5 Own method · 3 No basis given · 2 Partly supported · accuracy not yet measured
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In the paper
“We note that four HRDetect-low patients (4.7%) had mismatch-repair deficient (MMRd) tumors23”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Partly supportedcites [23] Davies, H. et al. Whole-genome sequencing reveals breast cancers with mismatch repair deficiency. Cancer Res. 77, 4755–4762 (2017). sourceExperimental — accuracy not yet measured
The Abstract reports 11 mismatch-repair-deficient tumors among 640 breast cancer patients. The paper does not report that four HRDetect-low patients had such tumors or give a 4.7% rate for that subgroup; HRDetect appears only in a cited reference (References, page unavailable). (LLM, conf=0.83)
plainn = 4- Asserted: passes — The authors put it forward as true.
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In the paper
“237 (93%) had WGS data of sufficient quality for comprehensive genomic profiling.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
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In the paper
“identified a germline SINE-VNTR-Alu (SVA) retrotransposon 1.8kb downstream of the first coding exon of BRCA1 in one patient, PD35958a.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had poorest outcomes.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“~4.7% were mismatch-repair-deficient”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“4665 patients were registered with invasive breast cancer in that period.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 4,665- Asserted: passes — The authors put it forward as true.
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In the paper
“of cases sequenced to 30-fold depth, 3% failed, whereas 11% of cases failed when sequenced to 15-fold coverage.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“distant relapse-free interval (HR=0.31, CI=0.13-0.76) compared to HRDetect-low”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (Hazard Ratio, HR=0.42, 95% confidence interval, CI=0.2-0.87)”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 13
- It may state two separate claims as one. 40
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Cancer whole genome sequencing (WGS) is now feasible, with thousands of matched tumor-normal pairs successfully sequenced to date, revealing novel biological insights2–4.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Partly supportedcites [2] Nik-Zainal, S. et al. Mutational processes molding the genomes of 21 breast cancers. Cell 149, 979–993 (2012). sourceExperimental — accuracy not yet measured
The Results (“Sequencing of Breast Cancers”) report whole-genome sequencing of 21 cancers with matched normal DNA, and the Discussion says the analysis yielded new insights into mutational processes. The paper does not support the claim that thousands of matched pairs had already been sequenced; it describes analyses of thousands of cancers as future work. (LLM, conf=0.90)
- Partly supportedcites [3] Nik-Zainal, S. et al. The life history of 21 breast cancers. Cell 149, 994–1007 (2012). sourceExperimental — accuracy not yet measured
The Results (Inference of Cancer Genome Evolution; page not provided) report whole-genome sequencing of 21 breast cancers, and the Introduction describes insights into their genomic evolution. These passages support the feasibility and biological-insights parts of the claim, but they do not establish that thousands of matched tumor–normal pairs had been sequenced. (LLM, conf=0.88)
- Partly supportedcites [4] Ryden, L. et al. Minimizing inequality in access to precision medicine in breast cancer by real-time population-based molecular analysis in the SCAN-B initiative. Br. J. Surg. 105, e158–e168 (2018). sourceExperimental — accuracy not yet measured
The References list a study of 560 breast cancer whole-genome sequences, supporting the feasibility of cancer WGS. But this paper’s Results report more than 7,500 tissue specimens processed for mRNA sequencing, not thousands of matched tumor–normal pairs sequenced by WGS. The cited passages also do not report novel biological insights from such pairs. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nine percent (n=408) were TNBCs, consistent with national TNBC incidence (~9% in 2015).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 408- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“High inclusion rates of ~85% have resulted in >13,500 patients recruited since 2010.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaindirectn = 13,500- Asserted: passes — The authors put it forward as true.
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In the paper
“These genomic features in the SCAN-B TNBC cohort were comparable to a previously reported WGS cohort8”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [8] Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47–54 (2016). source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“More than half of TNBCs (58.6%) were classified as HRDetect-high (exceeding predefined score of 0.7, predictive of BRCA1/BRCA2-deficiency9). 35.9% were classified as HRDetect-low (score <0.2), 5.5% fell within an HRD-intermediate category (score 0.2-0.7)”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [9] Davies, H. et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med. 23, 517–525 (2017). source
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, HRDetect-high scores were also observed in tumors with ER-staining (62.1% of cases with 1-10% ER-staining intensity), in middle-aged patients (58% of HRDetect-high were 50-70 years) and older patients (>70 years, 36.4% HRDetect-high cases), as well as tumors with non-basal-like gene expression profiles”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Among 254 patients, 2.4% had metastatic disease at diagnosis, and 6.7% received neoadjuvant treatment.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 254- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect-high classification was enriched in expected subgroups such as young patients (88.5% of women <50 years), high-grade tumors and a basal-like expression subtype”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“340 had enrolled into SCAN-B. Clinical re-review and availability of material for genomic/transcriptomic sequencing left 254 cases for matched tumor-normal WGS/RNAseq analysis”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 254- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although not significant for OS (HR=0.46, CI=0.19-1.13), it implies a potential effect with longer follow-up time”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As part of routine oncogenetic clinical screening, 49 of 254 recruited patients were previously screened for pathogenic germline variants in BRCA1 and BRCA2, with 12 positive findings (nine BRCA1- and three BRCA2-carriers).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
plainn = 254- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To note, the RNA sequencing cohort has a slightly lower inclusion of smaller tumors, due to that the SCAN-B tissue sampling is performed by a pathologist after enough tissue has been secured for routine diagnostics.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Five tumors had pathogenic germline PALB2 variants, three cases with c.509_510delGA variant (two biallelic, one monoallelic), one c.3239_3240delAA variant, one c.1039G>T variant. Four had wild-type allele inactivation through somatic pathogenic mutation in three cases and loss-of-heterozygosity in one instance.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 5- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“340 of these patients were enrolled in the SCAN-B study5,33,34 (ClinicalTrials.gov ID NCT02306096), which is a prospective, observational, population-based cohort study, from which 254 with concurrent RNAseq were selected for extensive clinical review and WGS.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
What the sources say
- Not checked yetcites [5] Saal, L. H. et al. The Sweden Cancerome Analysis Network-Breast (SCAN-B) initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine. Genome Med. 7, 20 (2015). source
- Not checked yetcites [33] Brueffer, C. et al. Clinical value of RNA sequencing-based classifiers for prediction of the five conventional breast cancer biomarkers: a report from the population-based multicenter Sweden Cancerome Analysis Network–Breast initiative. JCO Prec. Oncol. 2, 1–18 (2018). source
- Not checked yetcites [34] Chen, X. et al. TNBCtype: a subtyping tool for triple-negative breast cancer. Cancer Inf. 11, 147–156 (2012).
plainn = 340- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An improved OS was also observed (log-rank p=0.06, Figure 4C), albeit non-significant because of limited follow-up interval.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, wild-type allele LOH was noted and BRCA1 expression was markedly reduced.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelationalSingle case- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“E.g., for HRDetect-high cases (left heatmap) using a k=2 solution, >70% of these tumors are located in cluster 1, together with 40-70% of HRDetect-low samples (as seen in right heatmap).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(29% versus 14% for PTEN, 2.2% versus 25% for PIK3CA, and 0.7% versus 7.1% for AKT1 for HRDetect-high versus HRDetect-low, respectively).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that HRDetect classification amongst chemotherapy-treated patients provided independent prognostic information favouring a better outcome in HRDetect-high cases compared to HRDetect-low cases, for IDFS (Hazard ratio, HR=0.42, 95% confidence interval, CI=0.20-0.87) and DRFI (HR=0.31, CI=0.13-0.76).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For these patients, there were no differences observed in overall survival (OS), invasive disease-free survival (IDFS), or distant relapse-free interval (DRFI) between HRDetect-high and HRDetect-low categories (log-rank p>0.05).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we explored the HRDetect-intermediate cohort (scores 0.2-0.7, n=13, 5.5%).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plainn = 13- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on data from the national breast cancer quality registry in Sweden (NKBC), a background population of primary resectable breast cancers from the entire SCAN-B catchment region during September 1 2010 to March 31 2015 was identified (same time period from which the TNBC cases in the current study were selected), comprising of 8587 patients.”
- Also stated in: § Extended Data · plain
“Of these 8587 patients, 5417 were enrolled in SCAN-B, with 3520 patients having RNA sequencing data passing basic quality criteria.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
plainn = 3,520- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Extended Data · plain
In the paper
“the four biallelic PALB2 and five RAD51C cases (6.5% of HRDetect-high cases) consistently showed a BRCA2-null phenotype16 including elevated Substitution Signature 3, elevated Rearrangement Signatures 2 and 5, and no Rearrangement Signature 3”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [16] Polak, P. et al. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nat. Genet. 49, 1476–1486 (2017). source
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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In the paper
“The intermediate category is also enriched for hypermutators of a rearrangement signature of long tandem-duplications (RS1) (where RS1 is predominant, exceeding 100 RS1 rearrangements)26.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [26] Glodzik, D. et al. A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers. Nat. Genet. 49, 341–348 (2017). source
plaincorrelationaln = 32- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“148 of 153 patients (97%) were eligible for relapse analysis, of which 20% developed a relapse of some type”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
plainn = 153- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The broadened HRDetect-intermediate group had high prevalence of driver amplifications (75%, 24/32 cases) and harbored 47% of all CCNE1 amplifications.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelationaln = 32- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“When compared with HRDetect as reference, the “HRD assay” has a false negative rate of 13%, and 16% of CNA-based HRD-high cases were false positives.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [10] Paquet, E. R. & Hallett, M. T. Absolute assignment of breast cancer intrinsic molecular subtype. J. Natl Cancer Inst. 107, 357 (2014).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither was able to find distinct transcriptional patterns distinguishing HRDetect-high and HRDetect-low groups (Extended Data 4A-E). Likewise, exhaustive machine-learning-based exploration could also not achieve high prediction accuracy for HRDetect-high and HRDetect-low subgroups”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect classification persisted as a meaningful independent positive prognostic indicator for IDFS (HR=0.38, CI=0.17-0.85, p=0.02).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We noted that 83.5% of HRDetect-high tumors had scores exceeding 0.99, and nearly all were BRCA1/BRCA2-null tumors.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight substitution/indel driver genes were enriched, albeit non-discriminatory between groups (TP53, PTEN, ARID1B, MLLT4 for HRDetect-high, PIK3CA and AKT1 for HRDetect-low, and RB1 and FBXW7 for HRDetect-high and HRDetect-intermediate) (Chi-square test p<0.05”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“41% had ≥5 years of follow-up, 25% 4-5 years, 31% 2-4 years, and 4% <2 years of follow-up.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Patient cohort
plainn = 153- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Six were monoallelic for BRCA1/BRCA2 and had low tumor cellularity.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All patients with suspected breast cancer are offered recruitment without exception.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“The Sweden Cancerome Analysis Network – Breast (SCAN-B; ClinicalTrials.gov identifier NCT02306096)5 is an on-going population-based observational study currently involving nine hospitals in the South of Sweden serving nearly two million inhabitants or ~20% of the Swedish population.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [5] Saal, L. H. et al. The Sweden Cancerome Analysis Network-Breast (SCAN-B) initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine. Genome Med. 7, 20 (2015). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consequently, the HRD phenotype identified by HRDetect is enriched for but not restricted to typical basal-like tumors characteristic of young patients in TNBC.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“we applied a mutational-signature-based algorithm, HRDetect9 designed to detect “BRCA”ness or Homologous-recombination-repair deficiency (HRD)10, using default breast-cancer-specific parameters.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [9] Davies, H. et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat. Med. 23, 517–525 (2017). source
- Not checked yetcites [10] Paquet, E. R. & Hallett, M. T. Absolute assignment of breast cancer intrinsic molecular subtype. J. Natl Cancer Inst. 107, 357 (2014).
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“expression-based profiling (e.g., PAM50) and Integrative Clusters13,15 are not adequately able to discriminate HRDetect groups, suggesting that HRDetect provides a novel, independent angle to TNBC stratification.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
What the sources say
- Not checked yetcites [13] Lehmann, B. D. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Invest. 121, 2750–2767 (2011). source
- Not checked yetcites [15] Telli, M. L. et al. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin. Cancer Res. 22, 3764–3773 (2016). source
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The SCAN-B study was approved by the Regional Ethical Review Board in Lund, Sweden (applicable registration numbers 2009/658, 2015/277, 2016/742, 2018/267, and 2019/01252 for this study). All patients provided written informed consent prior to enrolment.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Online Methods > Ethics approval and consent to participate
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we show that PIK3CA/AKT1/PTEN mutations identified through targeted sequencing are differentially enriched in HRDetect categories, with different survival likelihoods.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In short, this study argues for WGS to improve TNBC patient stratification.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the HRDetect-intermediate group is a subset of tumors that are difficult to distinguish using customary genomic scar approaches or individual substitution signatures but are important to recognize because their idiosyncratic tumor biology is a harbinger of poor outcome and may be differently targetable in terms of therapeutics.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this suggests that HRDetect-low cases are deriving limited benefit from current standard-of-care, warranting a re-appraisal of systemic therapies for this now-identifiable subgroup with poor outcome.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Chemotherapy-treated and untreated HRDetect-low patients are comparable enough for their invasive disease-free survival to be compared.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Demonstration of the year to year representativity of molecular subtypes in breast cancer (PAM50, top panel) and administered treatments based on data from the NKBC (lower panel) for patients identified in D.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“PAM50 subtyping was performed using the AIMS method (Paquet et al.) (as for the TNBC cases in the current study) as this classifier is a single sample classifier that does not rely on a mean centering of gene expression data across a cohort (thus is not sensitive to e.g. potential bias in year to year inclusion).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
What the sources say
- Not checked yetcites Paquet et al.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The lower panels demonstrate the clinicopathological characteristics of the different subgroups in the consort diagram, demonstrating the representativity of the end RNA sequencing cohort compared to all enrolled SCAN-B patients and the total patient population in the catchment region.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Extended Data
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HRDetect is therefore more specific than current substitution signature and CNA approaches, while extending identification of HRD to a wider set of samples”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The 1000 Genomes dataset is a sufficient reference for judging whether the SVA insertion is novel.
“This specific mobile element has not been reported in the 1000 genomes dataset.”
The paper relies on this without support.
Chemotherapy-treated and untreated HRDetect-low patients are comparable enough for their invasive disease-free survival to be compared.
“chemotherapy-treated HRDetect-low patients had a similar IDFS to patients that did not receive adjuvant chemotherapy, in spite of superior fitness and lower age of diagnosis (75% <70 years)”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, we cannot formally exclude that these observations originate from differences in cohort inclusion criteria that could skew numbers (e.g. due to more recruitment of patients with triple negative breast cancer which has higher HRD rates12).”
From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD.”
From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [12]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“237 (93%) had WGS data of sufficient quality for comprehensive genomic profiling. Failure rate was influenced by sequencing depth: of cases sequenced to 30-fold depth, 3% failed, whereas 11% of cases failed when sequenced to 15-fold coverage.”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“254 cases for matched tumor-normal WGS/RNAseq analysis (170 at 30-fold and 84 at 15-fold sequence depth)”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“Of 139 HRDetect-high cases, 29 (21%) confirmed biallelic loss of BRCA1 or BRCA2 (i.e., 20 germline and 9 somatic with LOH of the wild-type parental allele) and 55 (40%) had BRCA1 hypermethylation with loss of the other parental allele (Figure 2A, note one case with concurrent BRCA2 biallelic alteration and BRCA1 hypermethylation).”
§ Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study > Introduction
“Causes for HRDetect-high scores in the remaining 46 (33%) samples were unclear.”
Citations
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Proteogenomic Markers of Chemotherapy Resistance and Response in Triple-Negative Breast Cancer
Anurag, M., Jaehnig, E. J., Krug, K., Lei, J. T., Bergstrom, E. J., Kim, B.-J., Vashist, T. D., Huynh, A. M. T., Dou, Y., Gou, X., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0200 · Cited by 139
“However, the majority of TNBC cases do not have an obvious hereditary explanation, and therefore the underlying DNA repair defects are more obscure (3).”
BackgroundGłodzik, D., Bosch, A., Hartman, J., Aine, M., Vallon‐Christersson, J., Reuterswärd, C., Karlsson, A., Mitra, S., Niméus, E., Holm, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17537-2 · Cited by 137
Self-citationMolecular subtypes and precision treatment of triple-negative breast cancer
Zhao, S., Zuo, W., Shao, Z., & Jiang, Y. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.03.194 · Cited by 140
The History of Early Breast Cancer Treatment
Ben-Dror, J., Shalamov, M. M., & Sonnenblick, A. (2022) · Genes · doi:10.3390/genes13060960 · Cited by 148
“These types of cancer are characterized by their deficiency in homologous recombination repair [75], which led researchers to investigate the efficacy of PARP (poly (adenosine diphosphate-ribose) polymerase) inhibitors in the treatment of BC patients with BRCA1/2 mutations.”
BackgroundStructural variations in cancer and the 3D genome
Dubois, F. P. B., Sidiropoulos, N., Weischenfeldt, J., & Beroukhim, R. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00488-9 · Cited by 112
Wang, X., Venet, D., Lifrange, F., Larsimont, D., Rediti, M., Stenbeck, L., Dupont, F., Rouas, G., Garcia, A. J., Craciun, L., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54145-w · Cited by 149
Sztupinszki, Z. M., Dióssy, M., Krzystanek, M., Börcsök, J., Pomerantz, M. M., Tisza, V., Spisák, S., Rusz, O., Csabai, I., Freedman, M. L., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2135 · Cited by 100
“The higher accuracy to identify truly HRD cases by WGS data was also demonstrated recently for breast cancer (10).”
BackgroundResultInfluentialStaaf, J., Häkkinen, J., Hegardt, C., Saal, L. H., Kimbung, S., Hedenfalk, I. A., Lien, T. G., Sørlie, T., Naume, B., Russnes, H. G., et al. (2022) · npj Breast Cancer · doi:10.1038/s41523-022-00465-3 · Cited by 96
Self-citationGrinda, T., Joyon, N., Lusque, A., Lefèvre, S., Arnould, L., Penault-Llorca, F. M., MacGrogan, G. M., Treilleux, I., Vincent‐Salomon, A., Haudebourg, J., et al. (2021) · npj Breast Cancer · doi:10.1038/s41523-021-00252-6 · Cited by 87
Therapeutic and prognostic insights from the analysis of cancer mutational signatures
Brady, S. W., Gout, A. M., & Zhang, J. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.08.007 · Cited by 82
Demircan, K., Bengtsson, Y., Sun, Q., Brange, A., Vallon‐Christersson, J., Rijntjes, E., Malmberg, M., Saal, L. H., Rydén, L., Borg, Å., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102145 · Cited by 85
Self-citationAberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion
Zeng, Q., Saghafinia, S., Chryplewicz, A., Fournier, N., Christe, L., Xie, Y., Guillot, J., Yucel, S., Li, P., Galván, J. A., et al. (2022) · Science · doi:10.1126/science.abl7207 · Cited by 92
“The human TNBC TMA was constructed at the University of Lund, in accordance with appropriate ethical approvals, as described previously (70).”
MethodHanssen, F., Garcia, M. U., Folkersen, L., Pedersen, A., Lescai, F., Jodoin, S., Miller, E., Seybold, M., Wacker, O., Smith, N. H., et al. (2024) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqae031 · Cited by 96
The DNA damage response pathway as a land of therapeutic opportunities for colorectal cancer
Mauri, G., Arena, S., Siena, S., Bardelli, A., & Bianchi, A. S. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.05.027 · Cited by 87
“* In cancer types other than colorectal cancer, “Signature 3” identify HRD and classify DDR alterations missense BRCA1/2 mutations; associated with BRCA1 and RAD51C silencing by promoter methylation; germline/somatic mutations of BRCA1/BRCA2; BRCA1 promoter hypermethylation; RAD51C hypermethylation or biallelic loss o…”
MethodPan, Z., Tan, C., Rao, L., Zhang, H., Zheng, Y., Liang, H., Ji, L., & Mao, Z. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202008624 · Cited by 84
Harvey-Jones, E. J., Raghunandan, M., Robbez‐Masson, L., Magraner-Pardo, L., Alaguthurai, T., Yablonovitch, A. L., Yen, J. L., Xiao, H. F., Brough, R., Frankum, J. R., et al. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.01.003 · Cited by 89
ShallowHRD: detection of homologous recombination deficiency from shallow whole genome sequencing
Eeckhoutte, A., Houy, A., Manié, É., Reverdy, M., Bièche, I., Marangoni, E., Goundiam, O., Vincent‐Salomon, A., Stoppa‐Lyonnet, D., Bidard, F., et al. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa261 · Cited by 72
Precision cancer medicine: Concepts, current practice, and future developments
Edsjö, A., Holmquist, L., Geoerger, B., Nowak, F., Gomon, G., Alix‐Panabières, C., Staaf, J., Ploeger, C., Lassen, U., Tourneau, C. L., et al. (2023) · Journal of Internal Medicine · doi:10.1111/joim.13709 · Cited by 91
Self-citationTischkowitz, M. D., Balmañà, J., Foulkes, W. D., James, P. A., Ngeow, J. Y. Y., Schmutzler, R. K., Voian, N. C., Wick, M. J., Stewart, D. R., & Pal, T. (2021) · Genetics in Medicine · doi:10.1038/s41436-021-01151-8 · Cited by 79
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“The SCAN-B study was approved by the Regional Ethical Review Board in Lund, Sweden (applicable registration numbers 2009/658, 2015/277, 2016/742, 2018/267, and 2019/ 01252 for this study) as outlined in (22).”
BackgroundMethodSelf-citationStok, C., Kok, Y. P., van den Tempel, N., & van Vugt, M. A. T. M. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab151 · Cited by 67
“For example, the HRDetect algorithm recently identified patients with triplenegative breast cancer (TNBC) that would benefit from PARP inhibitor treatment using mutational signature analysis of whole genome sequencing (WGS) data (19,214).”
MethodTargeting the DNA Damage Response Pathways and Replication Stress in Colorectal Cancer
Durinikova, E., Reilly, N. M., Buzo, K., Mariella, E., Chilà, R., Lorenzato, A., Dias, J. M. L., Grasso, G., Pisati, F., Lamba, S., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-0875 · Cited by 62
“More recently, advanced signature analysis in breast cancer through the HRDetect score has pointed out RAD51C loss as a reliable BRCAness biomarker (68), suggesting that similar molecular approaches could be attempted in patients with colorectal cancer to further improve patients’ selection.”
Self-citationCieśla, M., Ngoc, P. C. T., Cordero, E., Martínez, Á. S., Morsing, M., Muthukumar, S., Beneventi, G., Madej, M., Munita, R., Jönsson, T., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.01.034 · Cited by 62
Self-citationRandom Forest Modelling of High-Dimensional Mixed-Type Data for Breast Cancer Classification
Quist, J., Taylor, L., Staaf, J., & Grigoriadis, A. E. (2021) · Cancers · doi:10.3390/cancers13050991 · Cited by 67
“7) cases (98%, 100% and 99% in Cluster s1 and s3, and i6, respectively) (Figure 3) [8,9].”
BackgroundMethodInfluentialSelf-citationAli, R., McIntosh, S., & Savage, K. I. (2020) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22921 · Cited by 52
“with HRD.(22,23) A number of structural rearrangements may also lead”
BackgroundInfluentialMolecular analyses of triple-negative breast cancer in the young and elderly
Aine, M., Boyacı, C., Hartman, J., Häkkinen, J., Mitra, S., Campos, A. B., Niméus, E., Ehinger, A., Vallon‐Christersson, J., Borg, Å., et al. (2021) · Breast Cancer Research · doi:10.1186/s13058-021-01392-0 · Cited by 59
Self-citationThe Promise and Current Status of CDK12/13 Inhibition for the Treatment of Cancer
Tadesse, S., Duckett, D. R., & Monastyrskyi, A. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0240 · Cited by 58
Leibowitz, B. D., Dougherty, B. V., Bell, J. S. K., Kapilivsky, J., Michuda, J., Sedgewick, A. J., Munson, W., Chandra, T. A., Dry, J. R., Beaubier, N. T., et al. (2022) · BMC Cancer · doi:10.1186/s12885-022-09669-z · Cited by 58
Genome Protection by DNA Polymerase θ
Wood, R. D., & Doublié, S. (2022) · Annual Review of Genetics · doi:10.1146/annurev-genet-072920-041046 · Cited by 50
Roze, J. F., Monroe, G. R., Kutzera, J., Groeneweg, J. W., Stelloo, E., Paijens, S. T., Nijman, H. W., van Meurs, H. S., van Lonkhuijzen, L. R. C. W., Piek, J. M. J., et al. (2020) · Cancers · doi:10.3390/cancers12051308 · Cited by 54
“As a result, this coverage is sufficient to detect clonal mutations in our cohort of high tumor purity samples and is currently used in large cancer studies [45,46].”
BackgroundThe PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer
Abraham, J. E., Pinilla, K., Dayimu, A., Grybowicz, L., Demiris, N., Harvey, C., Drewett, L. M., Lucey, R., Fulton, A., Roberts, A. N., et al. (2024) · Nature · doi:10.1038/s41586-024-07384-2 · Cited by 53
Pérez‐Villatoro, F., Oikkonen, J., Casado, J., Chernenko, A., Gulhan, D., Tumiati, M., Li, Y., Lavikka, K., Hietanen, S., Hynninen, J., et al. (2022) · npj Precision Oncology · doi:10.1038/s41698-022-00339-8 · Cited by 46
Rustad, E. H., Nadeu, F., Angelopoulos, N., Ziccheddu, B., Bolli, N., Puente, X. S., Campo, E., Landgren, O., & Maura, F. (2021) · Communications Biology · doi:10.1038/s42003-021-01938-0 · Cited by 42
Sneha, S., Baker, S. C., Green, A. R., Storr, S. J., Aiyappa‐Maudsley, R., Martin, S. G., & Pors, K. (2021) · Biomedicines · doi:10.3390/biomedicines9030290 · Cited by 48
Accurate and sensitive mutational signature analysis with MuSiCal
Jin, H., Gulhan, D., Geiger, B., Ben-Isvy, D., Geng, D., Ljungström, V., & Park, P. J. (2024) · Nature Genetics · doi:10.1038/s41588-024-01659-0 · Cited by 54
Meijer, T. G., Nguyen, L., van Hoeck, A., Sieuwerts, A. M., Verkaik, N. S., Ladan, M. M., Ruigrok-Ritstier, K., van Deurzen, C. H. M., van de Werken, H. J. G., Lips, E. H., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02363-1 · Cited by 36
Self-citationPatsouris, A., Diop, K., Trédan, O., Nenciu, D., Gonçalvès, A., Arnedos, M., Sablin, M., Jézéquel, P., Jimenez, M., Droin, N. M., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.09.028 · Cited by 46
Homologous Recombination Deficiency Testing for BRCA-Like Tumors: The Road to Clinical Validation
Ladan, M. M., van Gent, D. C., & Jager, A. (2021) · Cancers · doi:10.3390/cancers13051004 · Cited by 45
Bai, X., Ni, J., Beretov, J., Graham, P., & Li, Y. (2021) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2021.06.001 · Cited by 50
“20 .”
The RECAP Test Rapidly and Reliably Identifies Homologous Recombination-Deficient Ovarian Carcinomas
van Wijk, L. M., Vermeulen, S., Meijers, M., van Diest, M. F., ter Haar, N. T., de Jonge, M. M., Solleveld‐Westerink, N., van Wezel, T., van Gent, D. C., Kroep, J. R., et al. (2020) · Cancers · doi:10.3390/cancers12102805 · Cited by 45
“These studies revealed that although both BRCA mutation status and HRD status provided information regarding the magnitude of the potential treatment benefit of a PARPi in a given patient population, these biomarkers did not sufficiently discriminate between patients that would or would not benefit from treatment [4,5…”
EXO1 protects BRCA1-deficient cells against toxic DNA lesions
van de Kooij, B., Schreuder, A., Pavani, R., Garzero, V., Uruci, S., Wendel, T. J., van Hoeck, A., Alonso, M. S. M., Everts, M., Koerse, D., et al. (2024) · Molecular Cell · doi:10.1016/j.molcel.2023.12.039 · Cited by 49
Ring, A. E., Kilburn, L., Pearson, A., Moretti, L., Afshari-Mehr, A., Wardley, A. M., Gürel, B., Macpherson, I. R., Riisnaes, R., Baird, R. D., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-1696 · Cited by 40
CDK12: cellular functions and therapeutic potential of versatile player in cancer
Pilařová, K., Herudek, J., & Blažek, D. (2020) · NAR Cancer · doi:10.1093/narcan/zcaa003 · Cited by 43
“About 50% of HGSOC and triple-negative breast cancer (TNBC) are defective in the HR pathway, with CDK12 being among several recurrently mutated DNA damage response genes (4,115).”
BackgroundBarroso‐Sousa, R., Forman, J., Collier, K. A., et al. (2022) · JCO Precision Oncology · doi:10.1200/po.21.00413 · Cited by 41
Chiang, Y., Lin, P., & Cheng, W. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.675972 · Cited by 38
Börcsök, J., Sztupinszki, Z. M., Bekele, R., Gao, S. P., Dióssy, M., Samant, A. S., Dillon, K. M., Tisza, V., Spisák, S., Rusz, O., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3316 · Cited by 35
Discovery through clinical sequencing in oncology
Donoghue, M. T. A., Schram, A. M., Hyman, D. M., & Taylor, B. S. (2020) · Nature Cancer · doi:10.1038/s43018-020-0100-0 · Cited by 38
Basyuni, S., Heskin, L., Degasperi, A., Black, D., Koh, C. C., Chmelova, L., Rinaldi, G., Bell, S., Grybowicz, L., Elgar, G., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51577-2 · Cited by 44
“Crucially, permitting FFPE WGS will not require changes to existing clinical pathways, nor should it interfere with existing FF or RNAlater sample collection.”
InfluentialSelf-citationvan Wijk, L. M., Nilas, A. B., Vrieling, H., & Vreeswijk, M. P. G. (2021) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2022.2020102 · Cited by 41
“Estimates based on various studies; i [50,106,111]; ii [74,78,94,112]; iii [80–83]; iv [92–95,105,119].”
BackgroundThe advance of adjuvant treatment for triple-negative breast cancer
Ge, J., Zuo, W., Chen, Y., Shao, Z., & Yu, K. (2021) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0752 · Cited by 45
Witz, A., Dardare, J., Betz, M., Michel, C., Husson, M., Gilson, P., Merlin, J., & Harlé, A. (2025) · Biomarker Research · doi:10.1186/s40364-025-00740-y · Cited by 52
“All genetic material, including coding and non-coding regions, is sequenced in this complete method [138, 139].”
Galland, L., Ballot, E., Mananet, H., Boidot, R., Lecuelle, J., Albuisson, J., Arnould, L., Desmoulins, I., Mayeur, D., Kaderbhaï, C., et al. (2022) · npj Breast Cancer · doi:10.1038/s41523-022-00395-0 · Cited by 36
Lehmann, B. D., Abramson, V. G., Dees, E. C., Shah, P. D., Ballinger, T. J., Isaacs, C. J., Santa-Maria, C. A., An, H., Ericsson, P. I. G., Sanders, M. E., et al. (2023) · JAMA Oncology · doi:10.1001/jamaoncol.2023.5424 · Cited by 40
TEQUILA-seq: a versatile and low-cost method for targeted long-read RNA sequencing
Wang, F., Xu, Y., Wang, R., Zhang, B. D., Smith, N., Notaro, A., Gaerlan, S., Kutschera, E., Kadash-Edmondson, K. E., Xing, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40083-6 · Cited by 38
“Genomic DNAanalysisoftumorsamples,includingbothWGS and targeted sequencing, has been broadly used in research and clinical settings 30,31,56,57 .”
Sztupinszki, Z. M., Dióssy, M., Börcsök, J., Prósz, A. G., Cornelius, N., Kjeldsen, M. K., Mirza, M. R., & Szállási, Z. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0981 · Cited by 37
“It was also suggested that combining the above listed mutational signatures into a composite signature may provide a more accurate measure of HRD (HRDetect) in breast cancer (17, 18).”
BackgroundSigurjonsdottir, G., Marchi, T. D., Ehinger, A., Hartman, J., Bosch, A., Staaf, J., Killander, F., & Niméus, E. (2023) · Breast Cancer Research · doi:10.1186/s13058-023-01724-2 · Cited by 37
Self-citationThe landscape of human SVA retrotransposons
Chu, C., Lin, E. W., Tran, A. V., Jin, H., Ho, N. I., Veit, A. D., Cortés‐Ciriano, I., Burns, K. H., Ting, D. T., & Park, P. J. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad821 · Cited by 33
“These include BRCA1 in breast cancer ( 6 ) ; TAF1 in X-linked dystonia-parkinsonism ( 7–9 ) ; FKTN in Fukuyama muscular dystrophy ( 10 ) , WDR66 in male infertility ( 11 ) , and several other genes ( 12–24 ) .”
BackgroundUpdate on triple‐negative breast cancers – highlighting subtyping update and treatment implication
Tsang, J. Y., & Tse, G. M.-K. (2022) · Histopathology · doi:10.1111/his.14784 · Cited by 36
“In fact, among the four mutational signature subtypes in breast cancer, more than half of TNBC were classified with the homologous recombination deficiency (HRD) mutational signature.(32,33) For a deeper understanding of breast cancer beyond gene profiling, a multi-omic approach with six different platforms has provid…”
BackgroundMolecular Testing in Breast Cancer
Sun, L., Wu, A. S.-H., Bean, G. R., Hagemann, I. S., & Lin, C. (2021) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2021.07.026 · Cited by 37
DNA damage response in breast cancer and its significant role in guiding novel precise therapies
Li, J., Jia, Z., Lin, D., Cao, H., Huang, Y., Xu, H., Xie, Z., Jiang, Y., Wang, X., & Liu, J. (2024) · Biomarker Research · doi:10.1186/s40364-024-00653-2 · Cited by 37
“HRD is found in up to 50% of TNBC cases, with g BRCA1/2 m causing 10–22% of these instances [5, 6, 36–40].”
BackgroundHomologous recombination deficiency: how genomic signatures are generated
Setton, J. S., Reis-Filho, J. S., & Powell, S. N. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2021.01.002 · Cited by 29
“Furthermore, a significant subset of tumors predicted to be HR-deficient by integrated signature analysis have been shown to lack identifiable genetic or epigenetic variants in HR genes [30,44], suggesting that signature analysis may increase the number of patients who could potentially benefit from HR-targeting cance…”
BackgroundResultWalsh, T., Casadei, S., Munson, K. M., Eng, M., Mandell, J. B., Gülsüner, S., & King, M. (2020) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2020-107320 · Cited by 31
Liao, G., Jiang, Z., Yang, Y., Zhang, C., Jiang, M., Zhu, J., Xu, L., Xie, A., Yan, M., Zhang, Y., et al. (2021) · BMC Medicine · doi:10.1186/s12916-021-02068-4 · Cited by 33
“Accumulated evidence has shown that HRD is associated with a better prognosis for patients with a variety of solid tumours [42, 43].”
BackgroundMolecular Heterogeneity and Evolution in Breast Cancer
Caswell-Jin, J. L., Lorenz, C., & Curtis, C. N. (2020) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-060220-014137 · Cited by 32
Pan-cancer landscape of homologous recombination deficiencyPreprint
Nguyen, L., Martens, J. W. M., van Hoeck, A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.13.905026 · Cited by 31
Dotolo, S., Abate, R. E., Roma, C., Guido, D., Preziosi, A., Tropea, B., Palluzzi, F., Giacò, L., & Normanno, N. (2022) · Biomedicines · doi:10.3390/biomedicines10092074 · Cited by 32
Clinical interpretation of whole-genome and whole-transcriptome sequencing for precision oncology
Jobanputra, V., Wrzeszczyński, K. O., Büttner, R., Caldas, C., Cuppen, E. P. J. G., Grimmond, S. M., Haferlach, T., Mullighan, C. G., Schuh, A., & Elemento, O. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.07.003 · Cited by 30
PALB2 Variants: Protein Domains and Cancer Susceptibility
Nepomuceno, T. C., Carvalho, M. A., Rodrigue, A., Simard, J., Masson, J., & Monteiro, Á. N. A. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.10.002 · Cited by 30
An overview of mutational and copy number signatures in human cancer
Steele, C. D., Pillay, N., & Alexandrov, L. B. (2022) · The Journal of Pathology · doi:10.1002/path.5912 · Cited by 27
“In an effort to generate a robust test for HRD, Davies et al built a predictive model for HRD – HRDetect – that incorporates SBS, indel, and rearrangement signatures, as well as CN genomic scars [65,66], which holds great promise but is restricted to WGS data.”
MethodResearch advances and new challenges in overcoming triple-negative breast cancer
Zong, Y., & Pegram, M. D. (2021) · Cancer Drug Resistance · doi:10.20517/cdr.2021.04 · Cited by 29
“This new model was recently validated in a Swedish cohort of 254 primary TNBC patient samples[60].”
MethodFei, H., Chen, S., & Xu, C. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.02.51 · Cited by 28
“However, it should be noted that the definite etiopathogenesis of TNBC is still unclear despite there were a great deal of researches on the mechanism in TNBC formation (10-12).”
BackgroundGenoREC: A Recommendation System for Interactive Genomics Data Visualization
Pandey, A., L’Yi, S., Wang, Q., Borkin, M. A., & Gehlenborg, N. (2022) · IEEE Transactions on Visualization and Computer Graphics · doi:10.1109/tvcg.2022.3209407 · Cited by 24
“For sparse quantitative and nominal values, we used various datasets including GWAS catalog [7], gene annotations [17], and somatic structural variants [49].”
MethodThe DNA methylation landscape of primary triple-negative breast cancer
Aine, M., Nacer, D. F., Arbajian, E., Veerla, S., Karlsson, A., Häkkinen, J., Johansson, H. J., Rosengren, F., Vallon‐Christersson, J., Borg, Å., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58158-x · Cited by 33
“DNA-based TNBC studies have focused on the strong association between TNBC and DNA repair de fi ciency, typically manifested as homologous recombination de fi ciency (HRD) caused predominantly by mutational or epigenetic alterations in BRCA1 6,7,15,16 , shaping tumor genomes over time through a mutational process that c…”
InfluentialSelf-citationQin, Y., Yuan, X., Cui, Z., Chen, W., Xu, S., Chen, K., Wang, F., Zheng, F., Ni, H., Shen, H., et al. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.115503 · Cited by 29
Caramelo, O. L., Silva, C., Caramelo, F. J., Frutuoso, C., Pinto, L., & Almeida‐Santos, T. (2022) · Hereditary Cancer in Clinical Practice · doi:10.1186/s13053-022-00242-0 · Cited by 27
“Breast cancers with germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants and biallelic inactivation show evidence of deficiency in homologous recombination repair [10, 11].”
BackgroundLam, R. A., Tien, T. Z., Joseph, C. R., et al. (2021) · Cancers · doi:10.3390/cancers13153875 · Cited by 26
“Homologous Recombination Deficiency Detect (HRDetect) mutationalsignature-based algorithm was used to classify tumours, with HRDetect-high patients having better invasive disease-free survival and distant relapse-free interval on adjuvant chemotherapy compared to HRDetect-low and HRDetect-intermediate having the poore…”
MethodZhang, J., Zhang, X., Li, Z., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.654672 · Cited by 26
“It is characterized by earlier recurrence, the tendency of metastasis, shortage of effective therapeutic drugs, and poor prognosis (2, 3).”
BackgroundQuiescent Cancer Cells Resist T Cell Attack by Forming an Immunosuppressive NichePreprint
Baldominos, P., Barbera-Mourelle, A., Barreiro, O., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3902781 · Cited by 26
Semaan, A., Bernard, V., Lee, J. J., Wong, J., Huang, J. H., Swartzlander, D. B., Stephens, B. M., Monberg, M. E., Weston, B. R., Bhutani, M. S., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2667 · Cited by 25
““HRDetect,” but the algorithm performed suboptimally with WES data because essential predictor components such as rearrangement signatures and indels analysis are restricted (35, 36).”
BackgroundMethodVidal, J. M., Tsiknakis, N., Staaf, J., Bosch, A., Ehinger, A., Niméus, E., Salgado, R., Bai, Y., Rimm, D. L., Hartman, J., et al. (2024) · EClinicalMedicine · doi:10.1016/j.eclinm.2024.102928 · Cited by 26
Self-citation
Metadata
- Authors
- Staaf, J., Glodzik, D., Bosch, A., Vallon-Christersson, J., Reuterswärd, C., Häkkinen, J., Degasperi, A., Amarante, T. D., Saal, L. H., Hegardt, C., Stobart, H., Ehinger, A., Larsson, C., Rydén, L., Loman, N., Malmberg, M., Kvist, A., Ehrencrona, H., Davies, H. R., Borg, Å., & Nik-Zainal, S.
- Affiliations
- Lund University (SE)
- University of Cambridge (GB)
- Corresponding author
- Staaf, Johan
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-09-30
- Volume
- 25
- Issue
- 10
- Pages
- 1526-1533
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6859071
- OpenAlex
- W2976898289
- Cited by
- 307
- References
- 38
- Citations by year
- 2026: 27 · 2025: 33 · 2024: 50 · 2023: 41 · 2022: 56 · 2021: 58 · 2020: 41 · 2019: 1
- FWCI
- 23.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (WT100183MA)
- Cancer Research UK (C60100/A25274, C60100/A23916)
- Cancerfonden (SIA190013)
- Sveriges Regering ((ALF) 2018/40612)
- Fru Berta Kamprads Stiftelse (FBKS-2018-4-146)
- Crafoordska Stiftelsen (20180543)
- Stiftelsen Konung Gustaf V:s Jubileumsfond (174271)
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- triple-negative breast cancer, whole genome sequencing, homologous recombination deficiency, mismatch repair deficiency, BRCA1, BRCA2, BRCA1 promoter hypermethylation, PALB2, adjuvant chemotherapy, disease-free survival, distant recurrence-free survival, prognostic factors, trial stratification
- MeSH terms
- Whole Genome Sequencing, Adult, Aged, Aged, 80 and over, Female, Genetics, Population, Humans, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Promoter Regions, Genetic, Germ-Line Mutation, Disease-Free Survival, DNA Methylation, Triple Negative Breast Neoplasms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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