The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers

Sońdka, Zbysław; Bamford, Sally; Cole, Charlotte G.; Ward, Sari; Dunham, Ian; Forbes, Simon

doi:10.1038/s41568-018-0060-1

Cited by 1,243 publications

(1,284 citation statements)

References 101 publications

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“…No putative driver (19) mutations or CNAs, were found at a significantly higher rate in claudin-low tumors, stratified by intrinsic subtype, than in non-claudin-low tumors of the same subtype ( Supplementary Table S2). Rather, claudinlow tumors tended to exhibit patterns of mutation/CNA associated with their intrinsic subtype.…”

Section: Characteristics Of Claudin-low Breast Tumor Are Delineated Bmentioning

confidence: 99%

“…Individually analyzed genomic aberrations were chosen according to the following criteria: (1) known function as early driver events (19,37); (2) among the most frequently observed aberrations in breast cancer (4, 5); (3) significantly different incidence between intrinsic subtypes (χ 2 -test P < 0.05 (4, 5)); (4) non-overlap with other selected events (i.e. only one CNA located on 8q24).…”

Section: Genomic Analysesmentioning

confidence: 99%

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Re-definition of claudin-low as a breast cancer phenotype

Fougner

Bergholtz

Norum

et al. 2019

Preprint

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The claudin-low breast cancer subtype is defined by gene expression characteristics and encompasses a remarkably diverse range of breast tumors. Here, we investigate genomic, transcriptomic, and clinical features of claudin-low breast tumors. We show that claudin-low is not simply a subtype analogous to the intrinsic subtypes (basal-like, HER2-enriched, luminal A, luminal B and normal-like) as previously portrayed, but is a complex additional phenotype which may permeate breast tumors of various intrinsic subtypes. Claudin-low tumors were distinguished by low genomic instability, mutational burden and proliferation levels, and high levels of immune and stromal cell infiltration. In other aspects, claudin-low tumors reflected characteristics of their intrinsic subtype. Finally, we have developed an alternative method for identifying claudin-low tumors and thereby uncovered potential weaknesses in the established claudin-low classifier. In sum, these findings elucidate the heterogeneity in claudin-low breast tumors, and substantiate a re-definition of claudin-low as a cancer phenotype.Contact informationC.F. christian.fougner@rr-research.noH.B. helga.bergholtz@rr-research.noJ.H.N. jens.henrik.norum@rr-research.noT.S. therese.sorlie@rr-research.no

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Section: Characteristics Of Claudin-low Breast Tumor Are Delineated Bmentioning

confidence: 99%

Section: Genomic Analysesmentioning

confidence: 99%

Re-definition of claudin-low as a breast cancer phenotype

Fougner

Bergholtz

Norum

et al. 2019

Preprint

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“…A total of 91 functional exonic mutations were obtained (Table S1), and five of the mutated genes, CASC5, NUTM1, PTPRC, KMT2C, and TBX3 are putative driver genes catalogued in the COSMIC Cancer Gene Census ( Figure S2). 35 Mutations in DNA repair genes are related to poor outcomes of prostate cancers, 12,36 but few are mutated in this prostate BCC sample such as BRCA2, consistent with good survival of this patient.…”

Section: Whole Exome Sequencing Reveals the Mutational Landscape Ofmentioning

confidence: 58%

Mutational and transcriptomic landscapes of a rare human prostate basal cell carcinoma

Long

Jiang

et al. 2020

The Prostate

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Background As a rare subtype of prostate carcinoma, basal cell carcinoma (BCC) has not been studied extensively and thus lacks systematic molecular characterization. Methods Here, we applied single‐cell genomic amplification and RNA‐Seq to a specimen of human prostate BCC (CK34βE12+/P63+/PAP−/PSA−). The mutational landscape was obtained via whole exome sequencing of the amplification mixture of 49 single cells, and the transcriptomes of 69 single cells were also obtained. Results The five putative driver genes mutated in BCC are CASC5, NUTM1, PTPRC, KMT2C, and TBX3, and the top three nucleotide substitutions are C>T, T>C, and C>A, similar to common prostate cancer. The distribution of the variant allele frequency values indicated that these single cells are from the same tumor clone. The 69 single cells were clustered into tumor, stromal, and immune cells based on their global transcriptomic profiles. The tumor cells specifically express basal cell markers like KRT5, KRT14, and KRT23 and epithelial markers EPCAM, CDH1, and CD24. The transcription factor covariance network analysis showed that the BCC tumor cells have distinct regulatory networks. By comparison with current prostate cancer datasets, we found that some of the bulk samples exhibit basal cell signatures. Interestingly, at single‐cell resolution the gene expression patterns of prostate BCC tumor cells show uniqueness compared with that of common prostate cancer‐derived circulating tumor cells. Conclusions This study, for the first time, discloses the comprehensive mutational and transcriptomic landscapes of prostate BCC, which lays a foundation for the understanding of its tumorigenesis mechanism and provides new insights into prostate cancers in general.

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“…All synonymous mutations were filtered out. Subsequently, only Tier 1 cancer gene census 81 genes that were altered in more than 20 cases were filtered using customized scripts and included in the analysis ( Supplementary Table 23).…”

Section: Analysis Of Associations Of Patient Features With Identifiedmentioning

confidence: 99%

“…Associations between presence or absence of a taxon and the number of non-synonymous genetic alterations in cancer gene consensus 81 genes of a patient were analyzed by student ttest for each cancer-taxon pair separately that was present in at least 10 patients. Additionally, a pan-cancer analysis was performed in the same way, using a linear regression model that was stratified by ICGC project.…”

Section: Association Between Taxa and Number Of Genetic Alterations Imentioning

confidence: 99%

An atlas of the tissue and blood metagenome in cancer reveals novel links between bacteria, viruses and cancer

Borchmann

2019

Preprint

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The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers

Cited by 1,243 publications

References 101 publications

Re-definition of claudin-low as a breast cancer phenotype

Re-definition of claudin-low as a breast cancer phenotype

Mutational and transcriptomic landscapes of a rare human prostate basal cell carcinoma

An atlas of the tissue and blood metagenome in cancer reveals novel links between bacteria, viruses and cancer

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