HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
Open accessAbstract
Approximately 1–5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1–5%) who could have selective therapeutic sensitivity to PARP inhibition.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
CHORD performs similarly to HRDetect based on predictions on the BRCA-EU dataset (AUROC = 0.98 for both models).
“We note that CHORD performs similarly to HRDetect based on predictions on the BRCA-EU dataset (AUROC = 0.98 for both models)9.”
From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [9]
The Results and Online Methods report an AUROC of 0.98 for HRDetect on the paper’s breast-cancer cohort (page numbers unavailable). They do not report CHORD predictions or a comparison on a dataset identified as BRCA-EU, so the claim that both models achieved 0.98 there is not supported by this source. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe genomic profile of solid tumors with BRCA inactivation is characterized by unique patterns of indels and structural variants.
“As consequence of these the genomic profile of these tumors is characterized by unique patterns of indels and structural variants.48”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [48]
The Results section, “Quantitatively defining features of ‘BRCA’ness” (page not provided), reports distinctive deletion and rearrangement patterns in BRCA1/BRCA2-null breast tumors. This supports the pattern described, but the evidence for both indels and structural variants is from breast tumors, not solid tumors generally. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThese features were used to develop a breast cancer-specific predictor of HRD known as HRDetect.
“These features were used to develop a breast cancer-specific predictor of HRD known as HRDetect9.”
From Pan-cancer landscape of homologous recombination deficiency. (2020) · cites this paper as [9]
HRDetect is a mutational-signature-based algorithm designed to detect BRCAness or homologous-recombination-repair deficiency, using default breast-cancer-specific parameters.
“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.”
From Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study (2019) · cites this paper as [9]
HRDetect classified 58.6% of the TNBCs as HRDetect-high, 35.9% as HRDetect-low, and 5.5% as intermediate.
“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)”
From Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study (2019) · cites this paper as [9]
Combining multiple mutational signatures or using HRDetect classified tumour HR status better than individual mutational signatures alone.
“We show that the combination of multiple mutational signatures or HRDetect [7] enabled better classification of the HR status in tumours than when using individual mutational signatures alone”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [7]
Loss of BRCA1, BRCA2, or PALB2 function produces a high mutation burden and specific signatures indicating defective homologous recombination.
“Loss of function of BRCA1, BRCA2 and PALB2 yield a high mutation burden and specific signatures inferring defective HR [7, 9, 10, 13].”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [7]
Loss of PALB2 function is linked to BRCA-deficient signatures.
“supporting previous studies linking loss of PALB2 function with BRCA-deficient signatures [7, 10, 13].”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [7]
WGS and HRDetect improve classification of tumours as BRCA-proficient or deficient compared with individual genomic parameters such as HRD score and substitution signature 3.
“We confirm the utility of WGS and HRDetect [7] to enhance the stratification of tumours as being BRCA-proficient versus deficient compared with individual genomic parameters (e.g. HRD score and substitution signature 3).”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
Regression shrinkage and selection via the lasso
Tibshirani, R. (1996) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1996.tb02080.x · Cited by 51,482 · see citing works
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660 · see citing works
Self-citationVelvet: Algorithms for de novo short read assembly using de Bruijn graphsPreprint
Zerbino, D. R., & Birney, E. (2008) · Genome Research · doi:10.1101/gr.074492.107 · Cited by 9,387 · see citing works
Self-citationTargeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683 · see citing works
Self-citationSpecific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198 · see citing works
Accurate whole human genome sequencing using reversible terminator chemistry
Bentley, D. R., Balasubramanian, S., Swerdlow, H. P., Smith, G. P., Milton, J., Brown, C. G., Hall, K. P., Evers, D. J., Barnes, C. L., Bignell, H. R., et al. (2008) · Nature · doi:10.1038/nature07517 · Cited by 3,684 · see citing works
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from <i>BRCA</i> Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634 · see citing works
Self-citationGenomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · cited 1× · see citing works
“Previously, base-substitution signature 3 was shown to distinguish germline BRCA1 / BRCA2 -null cancers from sporadic cancers in a small subset of breast cancers 29,30 and was subsequently extended to pancreatic 32,33 , ovarian 34 and stomach 35 cancers.”
BackgroundWhole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · cited 2× · see citing works
“Previously, base-substitution signature 3 was shown to distinguish germline BRCA1 / BRCA2 -null cancers from sporadic cancers in a small subset of breast cancers 29,30 and was subsequently extended to pancreatic 32,33 , ovarian 34 and stomach 35 cancers.”
BackgroundMethodAudeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279 · see citing works
Self-citationLandscape of somatic mutations in 560 breast cancer whole-genome sequences
Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., et al. (2016) · Nature · doi:10.1038/nature17676 · Cited by 2,218 · see citing works
Self-citationDNA-Repair Defects and Olaparib in Metastatic Prostate Cancer
Mateo, J., Carreira, S., Sandhu, S., Miranda, S., Mossop, H., Perez-Lopez, R., Nava Rodrigues, D., Robinson, D., Omlin, A., Tunariu, N., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1506859 · Cited by 2,185 · see citing works
Ye, K., Schulz, M. H., Long, Q., Apweiler, R., & Ning, Z. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp394 · Cited by 1,978 · see citing works
Mutational Processes Molding the Genomes of 21 Breast Cancers
Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.024 · Cited by 1,909 · see citing works
Self-citationOlaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer
Ledermann, J. A., Harter, P., Gourley, C., Friedlander, M. L., Vergote, I. B., Rustin, G. J. S., Scott, C. L., Meier, W., Shapira‐Frommer, R., Safra, T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105535 · Cited by 1,891 · see citing works
The DNA damage response and cancer therapy
Lord, C. J., & Ashworth, A. (2012) · Nature · doi:10.1038/nature10760 · Cited by 1,843 · see citing works
Tutt, A., Robson, M., Garber, J. E., Domchek, S. M., Audeh, M. W., Weitzel, J. N., Friedlander, M., Arun, B., Loman, N., Schmutzler, R. K., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60892-6 · Cited by 1,655 · see citing works
Self-citationWhole–genome characterization of chemoresistant ovarian cancer
Patch, A., Christie, E. L., Etemadmoghadam, D., Garsed, D. W., George, J., Fereday, S., Nones, K., Cowin, P. A., Alsop, K., Bailey, P. J., et al. (2015) · Nature · doi:10.1038/nature14410 · Cited by 1,551 · see citing works
The Life History of 21 Breast Cancers
Nik-Zainal, S., Van Loo, P., Wedge, D. C., Alexandrov, L. B., Greenman, C. D., Lau, K. W., Raine, K., Jones, D., Marshall, J., Ramakrishna, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.023 · Cited by 1,443 · see citing works
Self-citationDeciphering Signatures of Mutational Processes Operative in Human Cancer
Alexandrov, L. B., Nik‐Zainal, S., Wedge, D. C., Campbell, P. J., & Stratton, M. R. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.12.008 · Cited by 1,277 · see citing works
Self-citationLord, C. J., & Ashworth, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.21 · Cited by 1,257 · see citing works
Allele-specific copy number analysis of tumors
Loo, P. V., Nord, S., Lingjærde, O. C., Russnes, H. G., Rye, I. H., Sun, W., Weigman, V., Marynen, P., Zetterberg, A., Naume, B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009843107 · Cited by 1,231 · see citing works
Self-citationSecondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
Sakai, W., Swisher, E. M., Karlan, B. Y., Agarwal, M. K., Higgins, J., Friedman, C., Villegas, E., Jacquemont, C., Farrugia, D. J., Couch, F. J., et al. (2008) · Nature · doi:10.1038/nature06633 · Cited by 1,086 · see citing works
Clock-like mutational processes in human somatic cells
Alexandrov, L. B., Jones, P. H., Wedge, D. C., Sale, J. E., Campbell, P. J., Nik‐Zainal, S., & Stratton, M. R. (2015) · Nature Genetics · doi:10.1038/ng.3441 · Cited by 1,038 · see citing works
Self-citationResistance to therapy caused by intragenic deletion in BRCA2
Edwards, S. L., Brough, R., Lord, C. J., Natrajan, R., Vatcheva, R., Levine, D. A., Boyd, J., Reis-Filho, J. S., & Ashworth, A. (2008) · Nature · doi:10.1038/nature06548 · Cited by 1,011 · see citing works
Homologous Recombination and Human Health: The Roles of BRCA1, BRCA2, and Associated Proteins
Prakash, R., Zhang, Y., Feng, W., & Jasin, M. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016600 · Cited by 869 · see citing works
Abkevich, V., Timms, K. M., Hennessy, B. T., Potter, J., Carey, M. S., Meyer, L. A., Smith‐McCune, K., Broaddus, R. R., Lu, K. H., Chen, J., et al. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.451 · Cited by 818 · see citing works
Subclonal diversification of primary breast cancer revealed by multiregion sequencing
Yates, L. R., Gerstung, M., Knappskog, S., Desmedt, C., Gundem, G., Loo, P. V., Aas, T., Alexandrov, L. B., Larsimont, D., Davies, H., et al. (2015) · Nature Medicine · doi:10.1038/nm.3886 · Cited by 812 · see citing works
Self-citationAnglian Breast Cancer Study Group (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1407 · Cited by 602 · see citing works
Malone, K. E., Daling, J. R., Doody, D. R., Hsu, L., Bernstein, L., Coates, R. J., Marchbanks, P. A., Simon, M. S., McDonald, J. A., Norman, S. A., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0503 · Cited by 373 · see citing works
Two Decades After BRCA: Setting Paradigms in Personalized Cancer Care and Prevention
Couch, F. J., Nathanson, K. L., & Offit, K. (2014) · Science · doi:10.1126/science.1251827 · Cited by 342 · see citing works
Prevalence of Pathogenic BRCA1 Mutation Carriers in 5 US Racial/Ethnic Groups
John, E. M., Miron, A., Gong, G. D., Phipps, A. I., Felberg, A., Li, F. P., West, D. W., & Whittemore, A. S. (2007) · JAMA · doi:10.1001/jama.298.24.2869 · Cited by 329 · see citing works
Watkins, J. A., Irshad, S., Grigoriadis, A., & Tutt, A. N. (2014) · Breast Cancer Research · doi:10.1186/bcr3670 · Cited by 327 · see citing works
Self-citationGraeser, M., McCarthy, A., Lord, C. J., Savage, K., Hills, M., Salter, J., Orr, N., Parton, M., Smith, I. E., Reis-Filho, J. S., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1027 · Cited by 326 · see citing works
Cancer Suppression by the Chromosome Custodians, BRCA1 and BRCA2
Venkitaraman, A. R. (2014) · Science · doi:10.1126/science.1252230 · Cited by 290 · see citing works
Gene Expression Profiles of BRCA1-Linked, BRCA2-Linked, and Sporadic Ovarian Cancers
Jazaeri, A. A., Yee, C. J., Sotiriou, C. P., Brantley, K., Boyd, J. A., & Liu, E. T. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.13.990 · Cited by 282 · see citing works
Self-citationThe topography of mutational processes in breast cancer genomes
Morganella, S., Alexandrov, L. B., Głodzik, D., Zou, X., Davies, H. R., Staaf, J., Sieuwerts, A., Brinkman, A., Martin, S., Ramakrishna, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11383 · Cited by 236 · see citing works
Self-citationGenome-wide transcriptome profiling of homologous recombination DNA repair
Peng, G., Lin, C. C.-J., Mo, W., Dai, H., Park, Y., Kim, S. M., Peng, Y., Mo, Q., Siwko, S. K., Hu, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms4361 · Cited by 223 · see citing works
Vollebergh, M. A., Lips, E. H., Nederlof, P. M., Wessels, L. F. A., Schmidt, M. K., van Beers, E. H., Cornelissen, S., Holtkamp, M., Froklage, F. E., de Vries, E. G. E., et al. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq624 · Cited by 198 · see citing works
A mutational signature in gastric cancer suggests therapeutic strategies
Alexandrov, L. B., Nik‐Zainal, S., Siu, H. C., Leung, S. Y., & Stratton, M. R. (2015) · Nature Communications · doi:10.1038/ncomms9683 · Cited by 178 · see citing works
Self-citationLee, M. S., Green, R., Marsillac, S. M., Coquelle, N., Williams, R. S., Yeung, T., Foo, D., Hau, D., Hui, B., Monteiro, Á. N. A., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4563 · Cited by 170 · see citing works
Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH
Joosse, S. A., van Beers, E. H., Tielen, I. H. G., Horlings, H. M., Peterse, J. L., Hoogerbrugge, N., Ligtenberg, M. J. L., Wessels, L. F. A., Axwijk, P., Verhoef, S., et al. (2008) · Breast Cancer Research and Treatment · doi:10.1007/s10549-008-0117-z · Cited by 152 · see citing works
A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer: Table 1
Chappuis, P. O., Goffin, J., Wong, N., Perret, C., Ghadirian, P., Tonin, P. N., & Foulkes, W. D. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.8.608 · Cited by 147 · see citing works
Larsen, M. J., Kruse, T. A., Tan, Q., Lænkholm, A., Bak, M., Lykkesfeldt, A. E., Sørensen, K. P., Hansen, T. V. O., Ejlertsen, B., Gerdes, A., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064268 · Cited by 117 · see citing works
Natrajan, R., Wilkerson, P. M., Marchiò, C., Piscuoglio, S., Ng, C. K. Y., Wai, P. T., Lambros, M. B. K., Samartzis, E. P., Dedes, K. J., Frankum, J. R., et al. (2014) · The Journal of Pathology · doi:10.1002/path.4325 · Cited by 110 · see citing works
Ruscito, I., Dimitrova, D., Vasconcelos, I. I. M., Gellhaus, K., Schwachula, T., Bellati, F., Zeillinger, R., Benedetti-Panici, P., Vergote, I. B., Mahner, S., et al. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.05.001 · Cited by 103 · see citing works
Lips, E. H., Laddach, N., Savola, S. P., Vollebergh, M. A., Oonk, A. M. M., Imholz, A. L. T., Wessels, L. F. A., Wesseling, J., Nederlof, P. M., & Rodenhuis, S. (2011) · Breast Cancer Research · doi:10.1186/bcr3049 · Cited by 91 · see citing works
King, M. (2014) · Science · doi:10.1126/science.1251900 · Cited by 89 · see citing works
Rodriguez, A. A., Makris, A., Wu, M.-F., Rimawi, M. F., Froehlich, A. M., Dave, B., Hilsenbeck, S. G., Chamness, G. C., Lewis, M. T., Dobrolecki, L. E., et al. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-0983-z · Cited by 79 · see citing works
Stefánsson, Ó. A., Jonasson, J. G., Ólafsdóttir, K., et al. (2011) · Breast Cancer Research · doi:10.1186/bcr3020 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Drost, J., & Clevers, H. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0007-6 · Cited by 1,790 · see citing works
Adjuvant Olaparib for Patients with <i>BRCA1</i> - or <i>BRCA2</i> -Mutated Breast Cancer
Tutt, A. N. J., Garber, J. E., Kaufman, B., Viale, G., Fumagalli, D., Rastogi, P., Gelber, R. D., de Azambuja, E., Fielding, A., Balmaña, J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105215 · Cited by 1,729 · see citing works
Self-citationGarrido-Castro, A. C., Lin, N. U., & Polyak, K. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1177 · Cited by 1,451 · see citing works
State-of-the-art strategies for targeting the DNA damage response in cancer
Pilié, P. G., Tang, C., Mills, G. B., & Yap, T. A. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0114-z · Cited by 1,189 · see citing works
Molecular subtypes of pancreatic cancer
Collisson, E. A., Bailey, P., Chang, D. K., & Biankin, A. V. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0109-y · Cited by 892 · see citing works
Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer
Quigley, D. A., Dang, H. X., Zhao, S. G., Lloyd, P., Aggarwal, R., Alumkal, J. J., Foye, A., Kothari, V., Perry, M. D., Bailey, A. M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.039 · Cited by 733 · see citing works
A decade of clinical development of PARP inhibitors in perspective
Mateo, J., Lord, C. J., Serra, V., Tutt, A., Balmaña, J., Castroviejo-Bermejo, M., Cruz, C., Oaknin, A., Kaye, S. B., & de Bono, J. S. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz192 · Cited by 743 · see citing works
Self-citationAung, K. L., Fischer, S. E., Denroche, R. E., Jang, G.-H., Dodd, A., Creighton, S., Southwood, B., Liang, S.-B., Chadwick, D., Zhang, A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2994 · Cited by 618 · see citing works
Pan-cancer landscape of homologous recombination deficiency.
Nguyen, L., W. M. Martens, J., Van Hoeck, A., & Cuppen, E. (2020) · Nature communications · doi:10.1038/s41467-020-19406-4 · Cited by 532 · see citing works
“Table 1: (A) The number of ovarian and breast cancer HRD patients with BRCA1 promoter methylation as reported by Davies et al.[9] (from supplementary tables 1, 3, and 8) in comparison to (B) the number of CHORD-HRD ovarian and breast cancer patients without biallelic loss of the HRD associated genes (BRCA1/2, RAD51C,…”
BackgroundMethodInfluentialPerspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
Ding, L., Bailey, M. H., Porta-Pardo, E., Thorsson, V., Colaprico, A., Bertrand, D., Gibbs, D. L., Weerasinghe, A., Huang, K.-L., Tokheim, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.033 · Cited by 399 · see citing works
Degasperi, A., Amarante, T. D., Czarnecki, J., Shooter, S., Zou, X., Glodzik, D., Morganella, S., Nanda, A. S., Badja, C., Koh, G., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0027-5 · Cited by 304 · see citing works
Self-citationBiomarkers for Homologous Recombination Deficiency in Cancer
Hoppe, M. M., Sundar, R., Tan, D. S. P., & Jeyasekharan, A. D. (2018) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djy085 · Cited by 329 · see citing works
Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study
Staaf, J., Glodzik, D., Bosch, A., Vallon-Christersson, J., Reuterswärd, C., Häkkinen, J., Degasperi, A., Amarante, T. D., Saal, L. H., Hegardt, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0582-4 · Cited by 307 · see citing works
Self-citationBRCA locus-specific loss of heterozygosity in germline BRCA1 and BRCA2 carriers
Maxwell, K. N., Wubbenhorst, B., Wenz, B. M., De Sloover, D., Pluta, J., Emery, L., Barrett, A., Kraya, A. A., Anastopoulos, I. N., Yu, S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00388-9 · Cited by 296 · see citing works
Samstein, R. M., Krishna, C., Ma, X., Pei, X., Lee, K.-W., Makarov, V., Kuo, F., Chung, J., Srivastava, R. M., Purohit, T. A., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-00139-8 · Cited by 219 · see citing works
Genomic instability, inflammatory signaling and response to cancer immunotherapy
Chen, M., Linstra, R., & van Vugt, M. A. T. M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188661 · Cited by 166 · see citing works
Javle, M., Shacham-Shmueli, E., Xiao, L., Varadhachary, G., Halpern, N., Fogelman, D., Boursi, B., Uruba, S., Margalit, O., Wolff, R. A., et al. (2021) · JAMA Oncology · doi:10.1001/jamaoncol.2021.0006 · Cited by 127 · see citing works
Póti, Á., Gyergyák, H., Németh, E., Rusz, O., Tóth, S., Kovácsházi, C., Chen, D., Szikriszt, B., Spisák, S., Takeda, S., et al. (2019) · Genome Biology · doi:10.1186/s13059-019-1867-0 · Cited by 116 · see citing works
Self-citationA Subset of Colorectal Cancers with Cross-Sensitivity to Olaparib and Oxaliplatin
Arena, S., Corti, G., Durinikova, E., Montone, M., Reilly, N. M., Russo, M., Lorenzato, A., Arcella, P., Lazzari, L., Rospo, G., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2409 · Cited by 115 · see citing works
Portrait of a cancer: mutational signature analyses for cancer diagnostics
Van Hoeck, A., Tjoonk, N. H., van Boxtel, R., & Cuppen, E. (2019) · BMC Cancer · doi:10.1186/s12885-019-5677-2 · Cited by 107 · see citing works
Nones, K., Johnson, J., Newell, F., Patch, A. M., Thorne, H., Kazakoff, S. H., de Luca, X. M., Parsons, M. T., Ferguson, K., Reid, L. E., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz132 · Cited by 93 · see citing works
“We confirm the utility of WGS and HRDetect [7] to enhance the stratification of tumours as being BRCA-proficient versus deficient compared with individual genomic parameters (e.g. HRD score and substitution signature 3).”
InfluentialSelf-citationWhole-Genome Sequencing Reveals Breast Cancers with Mismatch Repair Deficiency
Davies, H., Morganella, S., Purdie, C. A., Jang, S. J., Borgen, E., Russnes, H., Glodzik, D., Zou, X., Viari, A., Richardson, A. L., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1083 · Cited by 99 · see citing works
Self-citationGenome Sequencing during a Patient’s Journey through Cancer
Nangalia, J., & Campbell, P. J. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1910138 · Cited by 66 · see citing works
Self-citationBiomarkers for Response to Immune Checkpoint Blockade
Ganesan, S., & Mehnert, J. (2020) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033604 · Cited by 51 · see citing works
Targeting the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Colorectal Cancer
Catalano, F., Borea, R., Puglisi, S., Boutros, A., Gandini, A., Cremante, M., Martelli, V., Sciallero, S., & Puccini, A. (2022) · Cancers · doi:10.3390/cancers14061388 · Cited by 44 · see citing works
Targeting DNA damage repair pathways in pancreas cancer
Crowley, F., Park, W., & O’Reilly, E. M. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09983-1 · Cited by 43 · see citing works
Williams, M. J., Oliphant, M. U. J., Au, V., Liu, C., Baril, C., O’Flanagan, C., Lai, D., Beatty, S., Van Vliet, M., Yiu, J. C., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01988-0 · Cited by 34 · see citing works
Villafañez, F., García, I. A., Carbajosa, S., Pansa, M. F., Mansilla, S., Llorens, M. C., Angiolini, V., Guantay, L., Jacobs, H., Madauss, K. P., et al. (2019) · Oncogene · doi:10.1038/s41388-019-0724-7 · Cited by 30 · see citing works
Funingana, I.-G., Reinius, M. A. V., Petrillo, A., Ang, J. E., & Brenton, J. D. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.02.008 · Cited by 23 · see citing works
Chao, A., Lai, C.-H., Wang, T.-H., Jung, S.-M., Lee, Y.-S., Chang, W.-Y., Yang, L.-Y., Ku, F.-C., Huang, H.-J., Chao, A.-S., et al. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1643-8 · Cited by 20 · see citing works
Evolution of Multiple Myeloma from a Genomic Perspective
Maura, F., Samur, M., & Munshi, N. (2026) · Blood · doi:10.1182/blood.2024026313 · Cited by 8 · see citing works
- Authors
- Davies, H., Glodzik, D., Morganella, S., Yates, L. R., Staaf, J., Zou, X., Ramakrishna, M., Martin, S., Boyault, S., Sieuwerts, A. M., Simpson, P. T., King, T. A., Raine, K., Eyfjord, J. E., Kong, G., Borg, Å., Birney, E., Stunnenberg, H. G., van de Vijver, M. J., Børresen-Dale, A.-L., Martens, J. W. M., Span, P. N., Lakhani, S. R., Vincent-Salomon, A., Sotiriou, C., Tutt, A., Thompson, A. M., Van Laere, S., Richardson, A. L., Viari, A., Campbell, P. J., Stratton, M. R., & Nik-Zainal, S.
- Affiliations
- Wellcome Sanger Institute (GB)
- Guy's and St Thomas' NHS Foundation Trust (GB)
- Lund University (SE)
- AstraZeneca (United Kingdom) (GB)
- Centre Léon Bérard (FR)
- Erasmus MC (NL)
- The University of Queensland (AU)
- Memorial Sloan Kettering Cancer Center (US)
- University of Iceland (IS)
- Hanyang University (KR)
- European Bioinformatics Institute (GB)
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Université Libre de Bruxelles (BE)
- Institute of Cancer Research (GB)
- The University of Texas MD Anderson Cancer Center (US)
- Brigham and Women's Hospital (US)
- Institut national de recherche en sciences et technologies du numérique (FR)
- ORCID
- Davies, Helen
- Morganella, Sandro
- Yates, Lucy R
- Staaf, Johan
- Zou, Xueqing
- Ramakrishna, Manasa
- Martin, Sancha
- Boyault, Sandrine
- Sieuwerts, Anieta M
- Simpson, Peter T
- King, Tari A
- Raine, Keiran
- Kong, Gu
- Borg, Åke
- Birney, Ewan
- Stunnenberg, Hendrik G
- Martens, John W M
- Span, Paul N
- Lakhani, Sunil R
- Sotiriou, Christos
- Tutt, Andrew
- Richardson, Andrea L
- Viari, Alain
- Stratton, Michael R
- Venue
- Nature Medicine
- Published
- 2017-03-13
- Volume
- 23
- Issue
- 4
- Pages
- 517-525
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC5833945
- OpenAlex
- W2596164112
- Semantic Scholar
- 832a0e972e79dbe5a66f63f24860aa273171515d
- Cited by
- 1,086
- References
- 51
- Citations by year
- 2026: 81 · 2025: 106 · 2024: 108 · 2023: 180 · 2022: 149 · 2021: 148 · 2020: 116 · 2019: 89 · 2018: 78 · 2017: 30
- FWCI
- 56.67
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Apollo
- Funders
- Breast Cancer Research Foundation
- Dana-Farber/Harvard Cancer Center (P50 CA168504)
- Wellcome Trust (077012/Z/05/Z, WT100183MA)
- Cancer Research UK (23916, 22932, 23433)
- National Institute for Health and Care Research
- European Commission (242006)
- National Research Foundation
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- National Research Foundation of Korea (2015R1A2A1A10052578)
- Institut National Du Cancer
- National Institutes of Health
- National Cancer Institute (CA168504, P50CA168504)
- 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
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- BRCA1 deficiency, BRCA2 deficiency, mutational signatures, homologous recombination deficiency, BRCAness, PARP inhibitors, platinum-based chemotherapy, breast cancer, ovarian cancer, pancreatic cancer, prediction model, LASSO logistic regression
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Breast Neoplasms, DNA Mutational Analysis, Female, Humans, Male, Models, Genetic, Mutation, Ovarian Neoplasms, Pancreatic Neoplasms, Logistic Models, Breast Neoplasms, Male, BRCA1 Protein, Area Under Curve, BRCA2 Protein
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
