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Cited by 293Genomics and Chromatin DynamicsChromatin Remodeling and CancerGenomic variations and chromosomal abnormalities

Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

Open access
Akdemir, Kadir C., Le, Victoria T., Chandran, Sahaana, Li, Yilong, Verhaak, Roel G., Beroukhim, Rameen, Campbell, Peter J., Chin, Lynda +1399 more·2020·Nature Genetics
DOI 10.1038/s41588-019-0564-yPMC PMC7058537

Published version of a preprint

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Abstract

Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.

AI snapshot

Written from the paper’s full text.

TL;DR

This pan-cancer PCAWG analysis examined 288,457 somatic structural variations across 2,658 cancers and found that TAD boundaries are recurrently disrupted in cancer-type-specific patterns, with duplications enriched at boundaries and deletions depleted. Although boundary-affecting SVs can alter chromatin folding and occasionally gene expression, only 14% of boundary deletions coincided with more than twofold expression changes.

Key findings

  • Across 2,658 cancers and 38 tumor types, 5.0% of deletions, 8.5% of inversions, 12.8% of duplications and 19.9% of complex events were boundary-affecting (BA); BA-duplications were enriched 1.43-fold (P < 10⁻⁴), while BA-deletions were depleted (0.87-fold, P = 0.052).
  • Most BA-SVs affected a single boundary: 74% of BA-deletions, 65% of BA-inversions, 71% of BA-duplications and 64% of BA-complex events; 98.4% of boundaries were affected in cancer genomes. Germline deletions affecting boundaries were rare (<0.1%; 6 of 924) versus somatic deletions (4.1%).
  • BA-SV burden varied by histology: leiomyosarcoma averaged 25 BA-SVs per sample, uterus adenocarcinoma 22, ovarian 20, esophageal 19 and breast adenocarcinoma 18, compared with a median of about 7 across all cancer samples; hematopoietic cancers had the lowest rates, and CNS-GBM showed lower-than-expected BA-SVs (P < 10⁻³).
  • Only 14% of all BA-deletions coincided with a twofold expression change; 25% of BA-deletions between repressed and active domains did so. Examples included 37-fold WNT4 upregulation, 26-fold SLC22A2 upregulation, 1.10-fold SLC2A10 change and sevenfold TRIM42 upregulation. In Hi-C data from four cancer cell lines, >90% of BA-SVs showed altered folding, and break-ends had 14.6-fold stronger contact frequency in cancer cells.

Methods

  • Used ICGC/TCGA PCAWG whole-genome sequencing data from 2,658 cancers across 38 tumor types and 288,457 high-confidence somatic SVs; classified deletions, inversions, duplications and complex rearrangements, focusing on short-range SVs (<2 Mb) and defining BA-SVs as those spanning a TAD boundary (~75 kb).
  • Called TAD boundaries from 25-kb-binned Hi-C data for GM12878, HMEC, IMR90, HUVEC and NHEK using an insulation-score approach, yielding 2,477 common boundaries; compared these with K562 and MCF7 boundaries and annotated domains using Roadmap Epigenome chromatin states, constitutive LADs and GTEx/ICGC expression data.
  • Generated high-resolution Hi-C data for four cancer cell lines (SW480, SNU-C1, HCC1954, OE33), integrated WGS SV calls, and analyzed contact maps, TAD fusions and neo-TAD formation.

Limitations

  • The paper states that cancer genomes may have other alterations affecting observed gene expression, including copy-number alterations and dysregulation of transcription factors, chromatin regulators or cis-regulatory elements, and that histology-specific matched control samples with WGS and chromatin organization data are needed.
  • The paper states that it focused on short-range SVs (<2 Mb) and intra-chromosomal events, excluding inter-chromosomal translocations; long-range SVs were not the main focus.
  • Evident from the text: Hi-C validation was limited to four cancer cell lines, and expression comparisons used the rest of the same cancer study samples rather than matched normal controls, so the functional impact of many BA-SVs remains uncertain.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/s41588-019-0564-y

Cites

77 of 77 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    There was a high overlap (85% for K562 and 83.4% for MCF7) between the common boundaries and TAD boundaries found in cancer cell lines.

    “We observed a high overlap with boundaries from a leukemia cell line K562 (ref. 17) and a breast cancer cell line MCF7 (ref. 20) (85% and 83.4%, respectively; Extended Data Fig. 1f,g).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [17] Rao, S. S. P. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014). source

      Not checked in the free run.

    • cites [20] Barutcu, A. R. et al. Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells. Genome Biol. 16, 214 (2015). source

      Not checked in the free run.

  • Findingown data

    Compared with the expected number of boundary disruptions based on randomly shuffled boundaries, BA-duplications were strongly enriched (P < 10−4, 1.43-fold enrichment).

    “Compared with the expected number of boundary disruptions based on randomly shuffled boundaries, these ratios are strongly enriched in BA-duplications (P < 10−4, 1.43-fold enrichment).”
    Quote in the paperSubstantial claim
  • Findingown data

    Across all cell types, a common set of 2,477 boundaries was identified.

    “Across all cell types, we identified a common set of 2,477 boundaries (Supplementary Table 1, Extended Data Fig. 1d).”
    Quote in the paperSubstantial claim
  • Findingown data

    The number of affected boundaries did not markedly change with the minimum length of the SVs.

    “The number of affected boundaries did not markedly change with the minimum length of the SVs (Fig. 1d, Extended Data Fig. 2c).”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was a significant (P < 10−6) overlap (a 50-kb distance was allowed) between TAD boundaries among all profiled cell types.

    “There was a significant (P < 10−6) overlap (a 50-kb distance was allowed) between TAD boundaries among all profiled cell types.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 17
  • The quote only partly states this claim. 1
  • May combine two claims. 26

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Length distributions of the BA-SVs were uniformly distributed.

    “Length distributions of the BA-SVs were uniformly distributed (Extended Data Fig. 2b).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    TAD boundaries called from 25-kb-binned Hi-C data for five human cell lines ranged from 3,926 to 4,690 per cell type.

    “As a result, a number of boundaries, which ranged from 3,926 to 4,690, were found for different cell types.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    BA-inversions and BA-complex events occurred at expected levels (P > 0.05) compared with shuffled TAD boundaries.

    “In contrast, we observed a depletion (0.87-fold enrichment, P = 0.052) in BA-deletions, whereas BA-inversions and BA-complex events occurred at expected levels (P > 0.05) compared with the shuffled TAD boundaries (Fig. 1c).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most BA-SVs targeted a single boundary; 74% of BA-deletions, 65% of BA-inversions, 71% of BA-duplications and 64% of BA-complex events affected a single boundary per variant.

    “Most of the BA-SVs targeted a single boundary; 74% of BA-deletions, 65% of BA-inversions, 71% of BA-duplications and 64% of BA-complex events affected a single boundary per variant (Fig. 1d).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    5.0%, 8.5%, 12.8% and 19.9% of all deletions, inversions, duplications and complex events were called BA events, respectively.

    “As a result, 5.0%, 8.5%, 12.8% and 19.9% of all deletions, inversions, duplications and complex events were called BA events, respectively (Fig. 1b).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    CTCF-binding sites and active promoter marks were enriched, whereas the heterochromatin state was depleted at the boundaries.

    “We observed that CTCF-binding sites and active promoter marks were enriched, whereas the heterochromatin state was depleted at the boundaries.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The majority (98.4%) of the boundaries were affected in cancer genomes, although a few boundaries were located in low-mappability regions.

    “The majority (98.4%) of the boundaries were affected in cancer genomes, although a few boundaries were located in the low-mappability regions of the genome.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The majority of deletions, inversions and duplications could be categorized as short-range; complex events tended to be longer in length.

    “The majority of deletions, inversions and duplications could be categorized as short-range; however, complex events tended to be longer in length (Extended Data Fig. 2a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Leiomyosarcoma and esophageal adenocarcinoma had a higher complex SV burden and, as a result, observed BA events were also mostly complex rearrangements.

    “For instance, leiomyosarcoma and esophageal adenocarcinoma had a higher complex SV burden and, as a result, observed BA events were also mostly complex rearrangements (Fig. 2b)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Ovarian, esophageal and breast adenocarcinomas also contained high numbers of BA-SVs with-on average-20, 19 and 18 BA-SVs per sample, respectively.

    “Ovarian, esophageal and breast adenocarcinomas also contained high numbers of BA-SVs with—on average—20, 19 and 18 BA-SVs per sample, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    BA-SV distributions on individual chromosomes were positively correlated with the number of boundaries (r2 = 0.68-0.92) and gene density (r2 = 0.7-0.85) on a given chromosome.

    “We surveyed the BA-SV distributions on individual chromosomes and observed a positive correlation with the number of boundaries (r2 = 0.68–0.92) and gene density (r2 = 0.7–0.85) on a given chromosome (Extended Data Fig. 4c,d).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Leiomyosarcoma and breast adenocarcinoma contained a higher number of BA-SVs compared with other cancer types, whereas leukemia samples had no BA-SVs per sample.

    “Again, leiomyosarcoma and breast adenocarcinoma contained a higher number of BA-SVs compared with other cancer types, whereas leukemia samples had no BA-SVs per sample (Extended Data Fig. 4a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Several discrepancies were observed between SVs detected in WGS data and Hi-C maps; these SV break-ends tended to be located in repetitive regions of the genome or overlapped with inter-chromosomal translocations.

    “By contrast, we observed several discrepancies between SVs detected in WGS data and Hi-C maps. These SV break-ends tended to be located in repetitive regions of the genome or overlapped with inter-chromosomal translocations (Extended Data Fig. 9a,c).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Deletions significantly occurred in LADs and duplications in inter-LADs, whereas SVs were less likely to occur between LADs and inter-LADs.

    “We observed that deletions significantly occurred in LADs and duplications in inter-LADs, whereas SVs were less likely to occur between LADs and inter-LADs (Extended Data Fig. 8d).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Repressed domains were larger in size and covered the majority of the genome compared with active domains, in agreement with previous TAD annotations.

    “Repressed domains were larger in size and covered the majority of the genome compared with active domains, in agreement with previous TAD annotations19,35 (Extended Data Fig. 7a,b).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Ho, J. W. K. et al. Comparative analysis of metazoan chromatin organization. Nature 512, 449–452 (2014). source

      Not checked in the free run.

    • cites [35] Sexton, T. & Yaffe, E. Chromosome folding: driver or passenger of epigenetic state? Cold Spring Harb. Perspect. Biol. 7, a018721 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Other potentially altered loops include a CTCF site near BCL6 in hepatocellular carcinoma and breast adenocarcinoma, and CLCN4 in colorectal adenocarcinomas.

    “Other potentially altered loops include a CTCF site near BCL6 in hepatocellular carcinoma and breast adenocarcinoma, and CLCN4 in colorectal adenocarcinomas (Extended Data Fig. 6a,b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Distributions of BA-SVs per chromosome were generally specific to the histology subtype; for example, chromosome 17 was affected predominantly by BA-complex events in breast and esophageal adenocarcinoma samples.

    “Notably, distributions of BA-SVs per chromosome were generally specific to the histology subtype; for example, chromosome 17 was affected predominantly by BA-complex events in breast and esophageal adenocarcinoma samples (Extended Data Fig. 5a,b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Duplications tended to span TADs and generally occurred within inter-LAD regions.

    “duplications tended to span TADs and generally occurred within inter-LAD regions”
    Quote in the paperSubstantial claim
    • Rests on an assumption: TAD boundaries identified in normal cell lines are representative of TAD boundaries in cancer cells.

  • May combine two claims.

    Findingown data

    The number of BA-SVs present in germline deletions and duplications was low and these events happened less than expected by chance.

    “We noticed that the number of BA-SVs present in germline deletions and duplications was low and these events happened less than expected by chance, which was estimated using a bootstrapping method.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Disruption of domain boundaries can result in ectopic interactions between neighboring domains and affect the regulation of nearby genes.

    “The disruption of domain boundaries can result in ectopic interactions between neighboring domains and affect the regulation of nearby genes5,9.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [5] Nora, E. P. et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381–385 (2012). source

      Not checked in the free run.

    • cites [9] Lupiáñez, D. G. et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161, 1012–1025 (2015). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    TADs are considered to represent functional domains because a given TAD encompasses the regulatory elements for the genes inside the same domain.

    “TADs are considered to represent functional domains because a given TAD encompasses the regulatory elements for the genes inside the same domain6,7.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] de Laat, W. & Duboule, D. Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502, 499–506 (2013). source

      Not checked in the free run.

    • cites [7] Vietri Rudan, M. et al. Comparative Hi-C reveals that CTCF underlies evolution of chromosomal domain architecture. Cell Rep. 10, 1297–1309 (2015). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several other studies have reported the deregulation of chromatin folding structures in different cancer types.

    “Several other studies have reported the deregulation of chromatin folding structures in different cancer types11,15,16.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [11] Weischenfeldt, J. et al. Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking. Nat. Genet. 49, 65–74 (2017). source

      Not checked in the free run.

    • cites [15] Hnisz, D. et al. Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science 351, 1454–1458 (2016). source

      Not checked in the free run.

    • cites [16] Flavahan, W. A. et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529, 110–114 (2016). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Deletions tended to occur within the same TAD, whereas duplications tended to span regions across different TADs.

    “Overall, these results suggest that deletions tended to occur within the same TAD, whereas duplications tended to span regions across different TADs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The impact of BA-SVs is varied substantially across tumor types and these events were reflective of overall SV burden and type.

    “Taken together, our findings show that the impact of BA-SVs is varied substantially across tumor types and these events were reflective of overall SV burden and type.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The region between KIAA1549 and BRAF has previously been implicated in pilocytic astrocytoma, producing an oncogenic fusion between these genes.

    “This region has previously been implicated in pilocytic astrocytoma, producing an oncogenic fusion between the aforementioned genes30.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Jones, D. T. W. et al. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res. 68, 8673–8677 (2008). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    These findings emphasize the cancer specificity of BA-SVs, in which active mechanisms lead to the overall SV burden and type in different tumor types yield potential changes in TAD structures, especially around cancer driver genes.

    “These findings emphasize the cancer specificity of BA-SVs, in which active mechanisms lead to the overall SV burden and type in different tumor types yield potential changes in TAD structures, especially around cancer driver genes.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    It has been suggested that SVs could lead to TAD fusions (also referred to as neo-TADs).

    “Furthermore, it has also been suggested that SVs could lead to TAD fusions40 (also referred to as neo-TADs3,4);”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [40] Dixon, J. R. et al. Integrative detection and analysis of structural variation in cancer genomes. Nat. Genet. 50, 1388–1398 (2018). source

      Not checked in the free run.

    • cites [3] Guelen, L. et al. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453, 948–951 (2008). source

      Not checked in the free run.

    • cites [4] Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376–380 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Chromatin folding perturbations can occur at various scales, include TADs and CTCF-CTCF chromatin loops in cancer genomes and recurrently altered boundaries are generally cancer-type specific.

    “Therefore, chromatin folding perturbations can occur at various scales, include TADs and CTCF–CTCF chromatin loops in cancer genomes and recurrently altered boundaries are generally cancer-type specific.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The observation of specific changes in Hi-C maps due to different SV types is consistent with findings from a recent study.

    “This observation of specific changes in Hi-C maps due to different SV types is consistent with findings from a recent study40.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Dixon, J. R. et al. Integrative detection and analysis of structural variation in cancer genomes. Nat. Genet. 50, 1388–1398 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Gene regulation in cancer genomes is multifactorial, although disruptions in chromatin folding domains may contribute to expression levels in certain cases, the effects of disruption do not always coincide with the expression changes.

    “These observations suggest that gene regulation in cancer genomes is multifactorial, although disruptions in chromatin folding domains may contribute to expression levels in certain cases, the effects of disruption do not always coincide with the expression changes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    SV break-ends reported by two different callers were included in the analysis.

    “SV breaks-ends reported by two different callers were included in this analysis.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Genes with low expression values (<0.1 FPKM) were filtered.

    “We filtered the genes with low expression values (<0.1 FPKM), as fold changes with those genes would be seemingly high for even small fluctuations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Changes in biological Hi-C replicates were detectable, suggesting that BA-SV effects are reproducible.

    “We could detect the changes in biological Hi-C replicates, suggesting that these BA-SV effects are reproducible”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Hi-C data from cancer cell lines accurately reflect chromatin folding in the corresponding primary tumors.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Hi-C was performed in duplicate.

    “Hi-C was performed using the in situ Hi-C protocol as previously described17 using 2–5 million cells per experiment that were digested with the MboI restriction enzyme and analyzed in duplicate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cancer genomes may have other alterations that could affect observed gene expression patterns, including copy-number alterations, dysregulation of transcription factors, chromatin regulators or cis-regulatory elements.

    “cancer genomes may have other alterations that could affect the observed gene expression patterns, including copy-number alterations, dysregulation of transcription factors, chromatin regulators or cis-regulatory elements44.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Lee, T. I. & Young, R. A. Transcriptional regulation and its misregulation in disease. Cell 152, 1237–1251 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The default 2-Mb window was truncated if there was another SV to avoid biases introduced by complex variants.

    “we truncated the default 2-Mb window if there was another SV to avoid biases introduced by complex variants.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Cases in which copy numbers were more than four for either the upstream or the downstream genes were removed.

    “We removed cases in which copy numbers are more than four for either the upstream or the downstream genes.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Regions for which the scaling factor was less than 0.1 were excluded to remove potential false-positive SV calls.

    “we excluded regions for which the scaling factor was less than 0.1 to remove potential false-positive calls.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Genes distal to the break-ends by more than 1 Mb were removed.

    “we removed genes that were distal to the break-ends by more than 1 Mb.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The low expression changes are consistent with the findings of recent studies.

    “which is consistent with the findings of recent studies42,43”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Ghavi-Helm, Y. et al. Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression. Nat. Genet. 51, 1272–1282 (2019). source

      Not checked in the free run.

    • cites [43] Despang, A. et al. Functional dissection of the Sox9–Kcnj2 locus identifies nonessential and instructive roles of TAD architecture. Nat. Genet. 51, 1263–1271 (2019). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    SVs can lead to cross-boundary interactions and potentially the formation of new chromatin folding domains based on the location of existing nearby TAD boundaries.

    “Our analysis revealed that intra-TAD/SV interactions were stronger than the inter-TAD/SV interactions, when controlling for genomic distance effects, which suggests that the SVs can lead to cross-boundary interactions and potentially the formation of new chromatin folding domains based on the location of existing nearby TAD boundaries (Fig. 5b).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    Disruption of folding domains could result in aberrant interactions between flanking domains and potentially contribute to the re-shaping of gene expression around the affected regions.

    “Disruption of folding domains could result in aberrant interactions between flanking domains and potentially contribute to the re-shaping of gene expression around the affected regions.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: TAD boundaries identified in normal cell lines are representative of TAD boundaries in cancer cells.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The cell lines were authenticated by comparing SV results from previous WGS datasets from the same cancer lines.

    “These cell lines were authenticated by comparing SV results from previous WGS datasets from the same cancer lines.”
    Quote in the paperNot a substantial claim
43 of 43

  • The paper relies on this without support.

    The frequency of domain disruptions in human cancers remains unclear.

    “However, the frequency of domain disruptions in human cancers remains unclear.”
    “Despite these recent examples of SVs that result in altered local enhancer–promoter landscapes, the frequency of such regulatory architecture rearrangements in cancer genomes remains unclear.”

  • The paper relies on this without support.

    Whether there are loci affected by potential changes in regulatory structure outside of those currently reported in the literature is unknown.

    “Similarly, whether there are loci affected by potential changes in regulatory structure outside of those currently reported in the literature is unknown.”

  • The paper relies on this without support.

    TAD boundaries identified in normal cell lines are representative of TAD boundaries in cancer cells.

    “Common TAD boundaries were identified for boundaries of all five cell-types (GM12878, HUVEC, IMR90, HMEC and NHEK) that occurred within two Hi-C bins or 50 kb in genomic range.”

  • The paper relies on this without support.

    Hi-C data from cancer cell lines accurately reflect chromatin folding in the corresponding primary tumors.

    “The colon cancer cell lines (SW480, SNU-C1) and breast adenocarcinoma cancer cell line (HCC1954) were obtained from the American Type Culture Collection and the esophageal adenocarcinoma (OE33) cell line was obtained from Sigma-Aldrich.”

  • The paper relies on this without support.

    The nearest genes to SV break-ends are the genes whose expression is affected by the SV.

    “We identified the nearest genes to the break-ends of BA-SVs as the nearest RefSeq genes that did not overlap with the break-ends.”
5 of 5

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 majority of TAD alterations did not affect gene expression.

    “However, as shown in Extended Data Fig. 3c, the majority of TAD alterations did not affect the expression of genes, consistent with a recent study in multiple cancer types26.”

    From Subtype-specific 3D genome alteration in acute myeloid leukaemia (2022) · cites this paper as [26]

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.

  • Germline boundary-deletion percentage does not match the reported count

    Major

    Six affected deletions out of 924 is approximately 0.65%, not less than 0.1%. This changes the reported magnitude of the germline rate used in the comparison with somatic deletions.

    Reported 0.1 · recomputed 0.649351

  • Conflicting GTEx sample counts

    Major

    The Results say the analysis used 2,921 cancer-free samples, whereas the Methods say it used 2,663.

  • Conflicting cancer type for the SLC2A10 example

    Minor

    The text identifies the sample in Fig. 4f as uterine adenocarcinoma, but the figure caption identifies it as ovarian adenocarcinoma.

3 of 3

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Akdemir, K. C., Le, V. T., Chandran, S., Li, Y., Verhaak, R. G., Beroukhim, R., Campbell, P. J., Chin, L., Dixon, J. R., Futreal, P. A., PCAWG Structural Variation Working Group, Akdemir, K. C., Alvarez, E. G., Baez-Ortega, A., Boutros, P. C., Bowtell, D. D. L., Brors, B., Burns, K. H., Campbell, P. J., Chan, K., Chen, K., Cortés-Ciriano, I., Dueso-Barroso, A., Dunford, A. J., Edwards, P. A., Estivill, X., Etemadmoghadam, D., Feuerbach, L., Fink, J. L., Frenkel-Morgenstern, M., Garsed, D. W., Gerstein, M., Gordenin, D. A., Haan, D., Haber, J. E., Hess, J. M., Hutter, B., Imielinski, M., Jones, D. T. W., Ju, Y. S., Kazanov, M. D., Klimczak, L. J., Koh, Y., Korbel, J. O., Kumar, K., Lee, E. A., Lee, J. J.-K., Li, Y., Lynch, A. G., Macintyre, G., Markowetz, F., Martincorena, I., Martinez-Fundichely, A., Meyerson, M., Miyano, S., Nakagawa, H., Navarro, F. C. P., Ossowski, S., Park, P. J., Pearson, J. V., Puiggròs, M., Rippe, K., Roberts, N. D., Roberts, S. A., Rodriguez-Martin, B., Schumacher, S. E., Scully, R., Shackleton, M., Sidiropoulos, N., Sieverling, L., Stewart, C., Torrents, D., Tubio, J. M. C., Villasante, I., Waddell, N., Wala, J. A., Weischenfeldt, J., Yang, L., Yao, X., Yoon, S.-S., Zamora, J., Zhang, C.-Z., PCAWG Consortium, Aaltonen, L. A., Abascal, F., Abeshouse, A., Aburatani, H., Adams, D. J., Agrawal, N., Ahn, K. S., Ahn, S.-M., Aikata, H., Akbani, R., Akdemir, K. C., Al-Ahmadie, H., Al-Sedairy, S. T., Al-Shahrour, F., Alawi, M., Albert, M., Aldape, K., Alexandrov, L. B., Ally, A., Alsop, K., Alvarez, E. G., Amary, F., Amin, S. B., Aminou, B., Ammerpohl, O., Anderson, M. J., Ang, Y., Antonello, D., Anur, P., Aparicio, S., Appelbaum, E. L., Arai, Y., Aretz, A., Arihiro, K., Ariizumi, S.-I., Armenia, J., Arnould, L., Asa, S., Assenov, Y., Atwal, G., Aukema, S., Auman, J. T., Aure, M. R. R., Awadalla, P., Aymerich, M., Bader, G. D., Baez-Ortega, A., Bailey, M. H., Bailey, P. J., Balasundaram, M., Balu, S., Bandopadhayay, P., Banks, R. E., Barbi, S., Barbour, A. P., Barenboim, J., Barnholtz-Sloan, J., Barr, H., Barrera, E., Bartlett, J., Bartolome, J., Bassi, C., Bathe, O. F., Baumhoer, D., Bavi, P., Baylin, S. B., Bazant, W., Beardsmore, D., Beck, T. A., Behjati, S., Behren, A., Niu, B., Bell, C., Beltran, S., Benz, C., Berchuck, A., Bergmann, A. K., Bergstrom, E. N., Berman, B. P., Berney, D. M., Bernhart, S. H., Beroukhim, R., Berrios, M., Bersani, S., Bertl, J., Betancourt, M., Bhandari, V., Bhosle, S. G., Biankin, A. V., Bieg, M., Bigner, D., Binder, H., Birney, E., Birrer, M., Biswas, N. K., Bjerkehagen, B., Bodenheimer, T., Boice, L., Bonizzato, G., De Bono, J. S., Boot, A., Bootwalla, M. S., Borg, A., Borkhardt, A., Boroevich, K. A., Borozan, I., Borst, C., Bosenberg, M., Bosio, M., Boultwood, J., Bourque, G., Boutros, P. C., Bova, G. S., Bowen, D. T., Bowlby, R., Bowtell, D. D. L., Boyault, S., Boyce, R., Boyd, J., Brazma, A., Brennan, P., Brewer, D. S., Brinkman, A. B., Bristow, R. G., Broaddus, R. R., Brock, J. E., Brock, M., Broeks, A., Brooks, A. N., Brooks, D., Brors, B., Brunak, S., Bruxner, T. J. C., Bruzos, A. L., Buchanan, A., Buchhalter, I., Buchholz, C., Bullman, S., Burke, H., Burkhardt, B., Burns, K. H., Busanovich, J., Bustamante, C. D., Butler, A. P., Butte, A. J., Byrne, N. J., Børresen-Dale, A.-L., Caesar-Johnson, S. J., Cafferkey, A., Cahill, D., Calabrese, C., Caldas, C., Calvo, F., Camacho, N., Campbell, P. J., Campo, E., Cantù, C., Cao, S., Carey, T. E., Carlevaro-Fita, J., Carlsen, R., Cataldo, I., Cazzola, M., Cebon, J., Cerfolio, R., Chadwick, D. E., Chakravarty, D., Chalmers, D., Chan, C. W. Y., Chan, K., Chan-Seng-Yue, M., Chandan, V. S., Chang, D. K., Chanock, S. J., Chantrill, L. A., Chateigner, A., Chatterjee, N., Chayama, K., Chen, H.-W., Chen, J., Chen, K., Chen, Y., Chen, Z., Cherniack, A. D., Chien, J., Chiew, Y.-E., Chin, S.-F., Cho, J., Cho, S., Choi, J. K., Choi, W., Chomienne, C., Chong, Z., Choo, S. P., Chou, A., Christ, A. N., Christie, E. L., Chuah, E., Cibulskis, C., Cibulskis, K., Cingarlini, S., Clapham, P., Claviez, A., Cleary, S., Cloonan, N., Cmero, M., Collins, C. C., Connor, A. A., Cooke, S. L., Cooper, C. S., Cope, L., Corbo, V., Cordes, M. G., Cordner, S. M., Cortés-Ciriano, I., Covington, K., Cowin, P. A., Craft, B., Craft, D., Creighton, C. J., Cun, Y., Curley, E., Cutcutache, I., Czajka, K., Czerniak, B., Dagg, R. A., Danilova, L., Davi, M. V., Davidson, N. R., Davies, H., Davis, I. J., Davis-Dusenbery, B. N., Dawson, K. J., De La Vega, F. M., De Paoli-Iseppi, R., Defreitas, T., Tos, A. P. D., Delaneau, O., Demchok, J. A., Demeulemeester, J., Demidov, G. M., Demircioğlu, D., Dennis, N. M., Denroche, R. E., Dentro, S. C., Desai, N., Deshpande, V., Deshwar, A. G., Desmedt, C., Deu-Pons, J., Dhalla, N., Dhani, N. C., Dhingra, P., Dhir, R., DiBiase, A., Diamanti, K., Ding, L., Ding, S., Dinh, H. Q., Dirix, L., Doddapaneni, H., Donmez, N., Dow, M. T., Drapkin, R., Drechsel, O., Drews, R. M., Serge, S., Dudderidge, T., Dueso-Barroso, A., Dunford, A. J., Dunn, M., Dursi, L. J., Duthie, F. R., Dutton-Regester, K., Eagles, J., Easton, D. F., Edmonds, S., Edwards, P. A., Edwards, S. E., Eeles, R. A., Ehinger, A., Eils, J., Eils, R., El-Naggar, A., Eldridge, M., Ellrott, K., Erkek, S., Escaramis, G., Espiritu, S. M. G., Estivill, X., Etemadmoghadam, D., Eyfjord, J. E., Faltas, B. M., Fan, D., Fan, Y., Faquin, W. C., Farcas, C., Fassan, M., Fatima, A., Favero, F., Fayzullaev, N., Felau, I., Fereday, S., Ferguson, M. L., Ferretti, V., Feuerbach, L., Field, M. A., Fink, J. L., Finocchiaro, G., Fisher, C., Fittall, M. W., Fitzgerald, A., Fitzgerald, R. C., Flanagan, A. M., Fleshner, N. E., Flicek, P., Foekens, J. A., Fong, K. M., Fonseca, N. A., Foster, C. S., Fox, N. S., Fraser, M., Frazer, S., Frenkel-Morgenstern, M., Friedman, W., Frigola, J., Fronick, C. C., Fujimoto, A., Fujita, M., Fukayama, M., Fulton, L. A., Fulton, R. S., Furuta, M., Futreal, P. A., Füllgrabe, A., Gabriel, S. B., Gallinger, S., Gambacorti-Passerini, C., Gao, J., Gao, S., Garraway, L., Garred, Ø., Garrison, E., Garsed, D. W., Gehlenborg, N., Gelpi, J. L. L., George, J., Gerhard, D. S., Gerhauser, C., Gershenwald, J. E., Gerstein, M., Gerstung, M., Getz, G., Ghori, M., Ghossein, R., Giama, N. H., Gibbs, R. A., Gibson, B., Gill, A. J., Gill, P., Giri, D. D., Glodzik, D., Gnanapragasam, V. J., Goebler, M. E., Goldman, M. J., Gomez, C., Gonzalez, S., Gonzalez-Perez, A., Gordenin, D. A., Gossage, J., Gotoh, K., Govindan, R., Grabau, D., Graham, J. S., Grant, R. C., Green, A. R., Green, E., Greger, L., Grehan, N., Grimaldi, S., Grimmond, S. M., Grossman, R. L., Grundhoff, A., Gundem, G., Guo, Q., Gupta, M., Gupta, S., Gut, I. G., Gut, M., Göke, J., Ha, G., Haake, A., Haan, D., Haas, S., Haase, K., Haber, J. E., Habermann, N., Hach, F., Haider, S., Hama, N., Hamdy, F. C., Hamilton, A., Hamilton, M. P., Han, L., Hanna, G. B., Hansmann, M., Haradhvala, N. J., Harismendy, O., Harliwong, I., Harmanci, A. O., Harrington, E., Hasegawa, T., Haussler, D., Hawkins, S., Hayami, S., Hayashi, S., Hayes, D. N., Hayes, S. J., Hayward, N. K., Hazell, S., He, Y., Heath, A. P., Heath, S. C., Hedley, D., Hegde, A. M., Heiman, D. I., Heinold, M. C., Heins, Z., Heisler, L. E., Hellstrom-Lindberg, E., Helmy, M., Heo, S. G., Hepperla, A. J., Heredia-Genestar, J. M., Herrmann, C., Hersey, P., Hess, J. M., Hilmarsdottir, H., Hinton, J., Hirano, S., Hiraoka, N., Hoadley, K. A., Hobolth, A., Hodzic, E., Hoell, J. I., Hoffmann, S., Hofmann, O., Holbrook, A., Holik, A. Z., Hollingsworth, M. A., Holmes, O., Holt, R. A., Hong, C., Hong, E. P., Hong, J. H., Hooijer, G. K., Hornshøj, H., Hosoda, F., Hou, Y., Hovestadt, V., Howat, W., Hoyle, A. P., Hruban, R. H., Hu, J., Hu, T., Hua, X., Huang, K.-L., Huang, M., Huang, M. N., Huang, V., Huang, Y., Huber, W., Hudson, T. J., Hummel, M., Hung, J. A., Huntsman, D., Hupp, T. R., Huse, J., Huska, M. R., Hutter, B., Hutter, C. M., Hübschmann, D., Iacobuzio-Donahue, C. A., Imbusch, C. D., Imielinski, M., Imoto, S., Isaacs, W. B., Isaev, K., Ishikawa, S., Iskar, M., Islam, S. M. A., Ittmann, M., Ivkovic, S., Izarzugaza, J. M. G., Jacquemier, J., Jakrot, V., Jamieson, N. B., Jang, G. H., Jang, S. J., Jayaseelan, J. C., Jayasinghe, R., Jefferys, S. R., Jegalian, K., Jennings, J. L., Jeon, S.-H., Jerman, L., Ji, Y., Jiao, W., Johansson, P. A., Johns, A. L., Johns, J., Johnson, R., Johnson, T. A., Jolly, C., Joly, Y., Jonasson, J. G., Jones, C. D., Jones, D. R., Jones, D. T. W., Jones, N., Jones, S. J. M., Jonkers, J., Ju, Y. S., Juhl, H., Jung, J., Juul, M., Juul, R. I., Juul, S., Jäger, N., Kabbe, R., Kahles, A., Kahraman, A., Kaiser, V. B., Kakavand, H., Kalimuthu, S., von Kalle, C., Kang, K. J., Karaszi, K., Karlan, B., Karlić, R., Karsch, D., Kasaian, K., Kassahn, K. S., Katai, H., Kato, M., Katoh, H., Kawakami, Y., Kay, J. D., Kazakoff, S. H., Kazanov, M. D., Keays, M., Kebebew, E., Kefford, R. F., Kellis, M., Kench, J. G., Kennedy, C. J., Kerssemakers, J. N. A., Khoo, D., Khoo, V., Khuntikeo, N., Khurana, E., Kilpinen, H., Kim, H. K., Kim, H.-L., Kim, H.-Y., Kim, H., Kim, J., Kim, J., Kim, J. K., Kim, Y., King, T. A., Klapper, W., Kleinheinz, K., Klimczak, L. J., Knappskog, S., Kneba, M., Knoppers, B. M., Koh, Y., Komorowski, J., Komura, D., Komura, M., Kong, G., Kool, M., Korbel, J. O., Korchina, V., Korshunov, A., Koscher, M., Koster, R., Kote-Jarai, Z., Koures, A., Kovacevic, M., Kremeyer, B., Kretzmer, H., Kreuz, M., Krishnamurthy, S., Kube, D., Kumar, K., Kumar, P., Kumar, S., Kumar, Y., Kundra, R., Kübler, K., Küppers, R., Lagergren, J., Lai, P. H., Laird, P. W., Lakhani, S. R., Lalansingh, C. M., Lalonde, E., Lamaze, F. C., Lambert, A., Lander, E., Landgraf, P., Landoni, L., Langerød, A., Lanzós, A., Larsimont, D., Larsson, E., Lathrop, M., Lau, L. M. S., Lawerenz, C., Lawlor, R. T., Lawrence, M. S., Lazar, A. J., Lazic, A. M., Le, X., Lee, D., Lee, D., Lee, E. A., Lee, H. J., Lee, J. J.-K., Lee, J.-Y., Lee, J., Lee, M. T. M., Lee-Six, H., Lehmann, K.-V., Lehrach, H., Lenze, D., Leonard, C. R., Leongamornlert, D. A., Leshchiner, I., Letourneau, L., Letunic, I., Levine, D. A., Lewis, L., Ley, T., Li, C., Li, C. H., Li, H. I., Li, J., Li, L., Li, S., Li, S., Li, X., Li, X., Li, X., Li, Y., Liang, H., Liang, S.-B., Lichter, P., Lin, P., Lin, Z., Linehan, W. M., Lingjærde, O. C., Liu, D., Liu, E. M., Liu, F.-F. F., Liu, F., Liu, J., Liu, X., Livingstone, J., Livitz, D., Livni, N., Lochovsky, L., Loeffler, M., Long, G. V., Lopez-Guillermo, A., Lou, S., Louis, D. N., Lovat, L. B., Lu, Y., Lu, Y.-J., Lu, Y., Luchini, C., Lungu, I., Luo, X., Luxton, H. J., Lynch, A. G., Lype, L., López, C., López-Otín, C., Ma, E. Z., Ma, Y., MacGrogan, G., MacRae, S., Macintyre, G., Madsen, T., Maejima, K., Mafficini, A., Maglinte, D. T., Maitra, A., Majumder, P. P., Malcovati, L., Malikic, S., Malleo, G., Mann, G. J., Mantovani-Löffler, L., Marchal, K., Marchegiani, G., Mardis, E. R., Margolin, A. A., Marin, M. G., Markowetz, F., Markowski, J., Marks, J., Marques-Bonet, T., Marra, M. A., Marsden, L., Martens, J. W. M., Martin, S., Martin-Subero, J. I., Martincorena, I., Martinez-Fundichely, A., Maruvka, Y. E., Mashl, R. J., Massie, C. E., Matthew, T. J., Matthews, L., Mayer, E., Mayes, S., Mayo, M., Mbabaali, F., McCune, K., McDermott, U., McGillivray, P. D., McLellan, M. D., McPherson, J. D., McPherson, J. R., McPherson, T. A., Meier, S. R., Meng, A., Meng, S., Menzies, A., Merrett, N. D., Merson, S., Meyerson, M., Meyerson, W., Mieczkowski, P. A., Mihaiescu, G. L., Mijalkovic, S., Mikkelsen, T., Milella, M., Mileshkin, L., Miller, C. A., Miller, D. K., Miller, J. K., Mills, G. B., Milovanovic, A., Minner, S., Miotto, M., Arnau, G. M., Mirabello, L., Mitchell, C., Mitchell, T. J., Miyano, S., Miyoshi, N., Mizuno, S., Molnár-Gábor, F., Moore, M. J., Moore, R. A., Morganella, S., Morris, Q. D., Morrison, C., Mose, L. E., Moser, C. D., Muiños, F., Mularoni, L., Mungall, A. J., Mungall, K., Musgrove, E. A., Mustonen, V., Mutch, D., Muyas, F., Muzny, D. M., Muñoz, A., Myers, J., Myklebost, O., Möller, P., Nagae, G., Nagrial, A. M., Nahal-Bose, H. K., Nakagama, H., Nakagawa, H., Nakamura, H., Nakamura, T., Nakano, K., Nandi, T., Nangalia, J., Nastic, M., Navarro, A., Navarro, F. C. P., Neal, D. E., Nettekoven, G., Newell, F., Newhouse, S. J., Newton, Y., Ng, A. W. T., Ng, A., Nicholson, J., Nicol, D., Nie, Y., Nielsen, G. P., Nielsen, M. M., Nik-Zainal, S., Noble, M. S., Nones, K., Northcott, P. A., Notta, F., O’Connor, B. D., O’Donnell, P., O’Donovan, M., O’Meara, S., O’Neill, B. P., O’Neill, J. R., Ocana, D., Ochoa, A., Oesper, L., Ogden, C., Ohdan, H., Ohi, K., Ohno-Machado, L., Oien, K. A., Ojesina, A. I., Ojima, H., Okusaka, T., Omberg, L., Ong, C. K., Ossowski, S., Ott, G., Ouellette, B. F. F., P’ng, C., Paczkowska, M., Paiella, S., Pairojkul, C., Pajic, M., Pan-Hammarström, Q., Papaemmanuil, E., Papatheodorou, I., Paramasivam, N., Park, J. W., Park, J.-W., Park, K., Park, K., Park, P. J., Parker, J. S., Parsons, S. L., Pass, H., Pasternack, D., Pastore, A., Patch, A.-M., Pauporté, I., Pea, A., Pearson, J. V., Pedamallu, C. S., Pedersen, J. S., Pederzoli, P., Peifer, M., Pennell, N. A., Perou, C. M., Perry, M. D., Petersen, G. M., Peto, M., Petrelli, N., Petryszak, R., Pfister, S. M., Phillips, M., Pich, O., Pickett, H. A., Pihl, T. D., Pillay, N., Pinder, S., Pinese, M., Pinho, A. V., Pitkänen, E., Pivot, X., Piñeiro-Yáñez, E., Planko, L., Plass, C., Polak, P., Pons, T., Popescu, I., Potapova, O., Prasad, A., Preston, S. R., Prinz, M., Pritchard, A. L., Prokopec, S. D., Provenzano, E., Puente, X. S., Puig, S., Puiggròs, M., Pulido-Tamayo, S., Pupo, G. M., Purdie, C. A., Quinn, M. C., Rabionet, R., Rader, J. S., Radlwimmer, B., Radovic, P., Raeder, B., Raine, K. M., Ramakrishna, M., Ramakrishnan, K., Ramalingam, S., Raphael, B. J., Rathmell, W. K., Rausch, T., Reifenberger, G., Reimand, J., Reis-Filho, J., Reuter, V., Reyes-Salazar, I., Reyna, M. A., Reynolds, S. M., Rheinbay, E., Riazalhosseini, Y., Richardson, A. L., Richter, J., Ringel, M., Ringnér, M., Rino, Y., Rippe, K., Roach, J., Roberts, L. R., Roberts, N. D., Roberts, S. A., Robertson, A. G., Robertson, A. J., Rodriguez, J. B., Rodriguez-Martin, B., Rodríguez-González, F. G., Roehrl, M. H. A., Rohde, M., Rokutan, H., Romieu, G., Rooman, I., Roques, T., Rosebrock, D., Rosenberg, M., Rosenstiel, P. C., Rosenwald, A., Rowe, E. W., Royo, R., Rozen, S. G., Rubanova, Y., Rubin, M. A., Rubio-Perez, C., Rudneva, V. A., Rusev, B. C., Ruzzenente, A., Rätsch, G., Sabarinathan, R., Sabelnykova, V. Y., Sadeghi, S., Sahinalp, S. C., Saini, N., Saito-Adachi, M., Saksena, G., Salcedo, A., Salgado, R., Salichos, L., Sallari, R., Saller, C., Salvia, R., Sam, M., Samra, J. S., Sanchez-Vega, F., Sander, C., Sanders, G., Sarin, R., Sarrafi, I., Sasaki-Oku, A., Sauer, T., Sauter, G., Saw, R. P. M., Scardoni, M., Scarlett, C. J., Scarpa, A., Scelo, G., Schadendorf, D., Schein, J. E., Schilhabel, M. B., Schlesner, M., Schlomm, T., Schmidt, H. K., Schramm, S.-J., Schreiber, S., Schultz, N., Schumacher, S. E., Schwarz, R. F., Scolyer, R. A., Scott, D., Scully, R., Seethala, R., Segre, A. V., Selander, I., Semple, C. A., Senbabaoglu, Y., Sengupta, S., Sereni, E., Serra, S., Sgroi, D. C., Shackleton, M., Shah, N. C., Shahabi, S., Shang, C. A., Shang, P., Shapira, O., Shelton, T., Shen, C., Shen, H., Shepherd, R., Shi, R., Shi, Y., Shiah, Y.-J., Shibata, T., Shih, J., Shimizu, E., Shimizu, K., Shin, S. J., Shiraishi, Y., Shmaya, T., Shmulevich, I., Shorser, S. I., Short, C., Shrestha, R., Shringarpure, S. S., Shriver, C., Shuai, S., Sidiropoulos, N., Siebert, R., Sieuwerts, A. M., Sieverling, L., Signoretti, S., Sikora, K. O., Simbolo, M., Simon, R., Simons, J. V., Simpson, J. T., Simpson, P. T., Singer, S., Sinnott-Armstrong, N., Sipahimalani, P., Skelly, T. J., Smid, M., Smith, J., Smith-McCune, K., Socci, N. D., Sofia, H. J., Soloway, M. G., Song, L., Sood, A. K., Sothi, S., Sotiriou, C., Soulette, C. M., Span, P. N., Spellman, P. T., Sperandio, N., Spillane, A. J., Spiro, O., Spring, J., Staaf, J., Stadler, P. F., Staib, P., Stark, S. G., Stebbings, L., Stefánsson, Ó. A., Stegle, O., Stein, L. D., Stenhouse, A., Stewart, C., Stilgenbauer, S., Stobbe, M. D., Stratton, M. R., Stretch, J. R., Struck, A. J., Stuart, J. M., Stunnenberg, H. G., Su, H., Su, X., Sun, R. X., Sungalee, S., Susak, H., Suzuki, A., Sweep, F., Szczepanowski, M., Sültmann, H., Yugawa, T., Tam, A., Tamborero, D., Tan, B. K. T., Tan, D., Tan, P., Tanaka, H., Taniguchi, H., Tanskanen, T. J., Tarabichi, M., Tarnuzzer, R., Tarpey, P., Taschuk, M. L., Tatsuno, K., Tavaré, S., Taylor, D. F., Taylor-Weiner, A., Teague, J. W., Teh, B. T., Tembe, V., Temes, J., Thai, K., Thayer, S. P., Thiessen, N., Thomas, G., Thomas, S., Thompson, A., Thompson, A. M., Thompson, J. F. F., Thompson, R. H., Thorne, H., Thorne, L. B., Thorogood, A., Tiao, G., Tijanic, N., Timms, L. E., Tirabosco, R., Tojo, M., Tommasi, S., Toon, C. W., Toprak, U. H., Torrents, D., Tortora, G., Tost, J., Totoki, Y., Townend, D., Traficante, N., Treilleux, I., Trotta, J.-R., Trümper, L. H. P., Tsao, M., Tsunoda, T., Tubio, J. M. C., Tucker, O., Turkington, R., Turner, D. J., Tutt, A., Ueno, M., Ueno, N. T., Umbricht, C., Umer, H. M., Underwood, T. J., Urban, L., Urushidate, T., Ushiku, T., Uusküla-Reimand, L., Valencia, A., Van Den Berg, D. J., Van Laere, S., Van Loo, P., Van Meir, E. G., Van den Eynden, G. G., Van der Kwast, T., Vasudev, N., Vazquez, M., Vedururu, R., Veluvolu, U., Vembu, S., Verbeke, L. P. C., Vermeulen, P., Verrill, C., Viari, A., Vicente, D., Vicentini, C., VijayRaghavan, K., Viksna, J., Vilain, R. E., Villasante, I., Vincent-Salomon, A., Visakorpi, T., Voet, D., Vyas, P., Vázquez-García, I., Waddell, N. M., Waddell, N., Wadelius, C., Wadi, L., Wagener, R., Wala, J. A., Wang, J., Wang, J., Wang, L., Wang, Q., Wang, W., Wang, Y., Wang, Z., Waring, P. M., Warnatz, H.-J., Warrell, J., Warren, A. Y., Waszak, S. M., Wedge, D. C., Weichenhan, D., Weinberger, P., Weinstein, J. N., Weischenfeldt, J., Weisenberger, D. J., Welch, I., Wendl, M. C., Werner, J., Whalley, J. P., Wheeler, D. A., Whitaker, H. C., Wigle, D., Wilkerson, M. D., Williams, A., Wilmott, J. 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Affiliations
  • Salk Institute for Biological Studies (US)
  • The Jackson Laboratory for Genomic Medicine (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • The University of Melbourne (AU)
  • University of Cambridge (GB)
  • Universidade de Vigo (ES)
  • Harvard University (US)
  • Dana-Farber Cancer Institute (US)
  • Barcelona Supercomputing Center (ES)
  • The University of Queensland (AU)
  • Broad Institute (US)
  • University of California, Los Angeles (US)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • National Center for Tumor Diseases (DE)
  • Weill Cornell Medicine (US)
  • Johns Hopkins University (US)
  • Washington State University (US)
  • University of Ottawa (CA)
  • Charité – Universitätsmedizin Berlin (DE)
  • University of Chicago (US)
  • Heidelberg University (DE)
  • German Cancer Research Center (DE)
  • Bar-Ilan University (IL)
  • Yale University (US)
  • University of California, Santa Cruz (US)
  • Brandeis University (US)
  • Universitat Pompeu Fabra (ES)
  • Massachusetts General Hospital (US)
  • Wellcome Sanger Institute (GB)
  • Korea Advanced Institute of Science and Technology (KR)
  • Boston Children's Hospital (US)
  • Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (RU)
  • National Institute of Environmental Health Sciences (US)
  • Seoul National University (KR)
  • European Molecular Biology Laboratory (DE)
  • University of St Andrews (GB)
  • RIKEN Center for Integrative Medical Sciences (JP)
  • Institute of Medical Science, The University of Tokyo (JP)
  • Beth Israel Deaconess Medical Center (US)
  • University of Copenhagen (DK)
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2020-02-05
Volume
52
Issue
3
Pages
294-305
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/s41588-019-0564-y
PMC
PMC7058537
OpenAlex
W3004613412
Semantic Scholar
e893e2a1e7f6f04cc9647d57e541b9fc2f97c23b
Cited by
283
References
76
Citations by year
2026: 23 · 2025: 36 · 2024: 43 · 2023: 43 · 2022: 53 · 2021: 64 · 2020: 17 · 2019: 2 · 2018: 2
FWCI
15.01
Type
journal article
Language
en
Update notices
correction (2023-03-21)
Open access
Licence
Locations
  • Nature Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • Lund University Publications (Lund University) (submittedVersion)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion, cc-by)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • St Andrews Research Repository (St Andrews Research Repository) (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Cancer Prevention and Research Institute of Texas (R1205)
  • Welch Foundation (G-0040)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
chromatin folding, topologically associating domains, somatic structural variants, chromatin boundaries, cancer genomics
MeSH terms
Chromatin, Humans, Neoplasms, Gene Rearrangement, Genome, Human, Gene Expression Regulation, Neoplastic, Genomic Structural Variation

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