Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Abstract

The Catalogue of Somatic Mutations in Cancer (COSMIC) Cancer Gene Census (CGC) is an expert-curated description of the genes driving human cancer that is used as a standard in cancer genetics across basic research, medical reporting and pharmaceutical development. After a major expansion and complete re-evaluation, the 2018 CGC describes in detail the effect of 719 cancer-driving genes. The recent expansion includes functional and mechanistic descriptions of how each gene contributes to disease generation in terms of the key cancer hallmarks and the impact of mutations on gene and protein function. These functional characteristics depict the extraordinary complexity of cancer biology and suggest multiple cancer-related functions for many genes, which are often highly tissue-dependent or tumour stage-dependent. The 2018 CGC encompasses a second tier, describing an expanding list of genes (currently 145) from more recent cancer studies that show supportive but less detailed indications of a role in cancer.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Functional classes of genes involved in fusions and their classification within the Cancer Gene Census.
Fig. 2: Tiers of the Cancer Gene Census.
Fig. 3: Quantification of the three classes of cancer genes in the Cancer Gene Census tiers.
Fig. 4: Graphical summary of hallmarks of cancer-related functions of PTEN presented on the Cancer Gene Census website.

References

  1. Futreal, P. A. et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177–183 (2004). This publication describes the first version of the CGC, presenting 291 genes causally implicated in cancer and characterizing their alterations.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Department of Health & Social Care. Whole Genome Analysis — 100,000 Genomes Project Cancer Programme. Genomics England https://www.genomicsengland.co.uk/information-for-gmc-staff/cancer-programme/genome-analysis (2017).

  3. Patel, M. N., Halling-Brown, M. D., Tym, J. E., Workman, P. & Al-Lazikani, B. Objective assessment of cancer genes for drug discovery. Nat. Rev. Drug Discov. 12, 35–50 (2013).

    CAS  PubMed  Google Scholar 

  4. Koscielny, G. et al. Open Targets: a platform for therapeutic target identification and validation. Nucleic Acids Res. 45, D985–D994 (2017).

    CAS  PubMed  Google Scholar 

  5. Ramos, A. H. et al. Oncotator: cancer variant annotation tool. Hum. Mutat. 36, E2423–E2429 (2015).

    PubMed  PubMed Central  Google Scholar 

  6. Van den Eynden, J., Fierro, A. C., Verbeke, L. P. & Marchal, K. SomInaClust: detection of cancer genes based on somatic mutation patterns of inactivation and clustering. BMC Bioinformatics 16, 125 (2015).

    PubMed  PubMed Central  Google Scholar 

  7. Schroeder, M. P., Rubio-Perez, C., Tamborero, D., Gonzalez-Perez, A. & Lopez-Bigas, N. OncodriveROLE classifies cancer driver genes in loss of function and activating mode of action. Bioinformatics 30, i549–i555 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Tamborero, D., Gonzalez-Perez, A. & Lopez-Bigas, N. OncodriveCLUST: exploiting the positional clustering of somatic mutations to identify cancer genes. Bioinformatics 29, 2238–2244 (2013).

    CAS  PubMed  Google Scholar 

  9. Forbes, S. A. et al. COSMIC: somatic cancer genetics at high-resolution. Nucleic Acids Res. 45, D777–D783 (2017).

    CAS  PubMed  Google Scholar 

  10. Forbes, S. A. et al. COSMIC: high-resolution cancer genetics using the catalogue of somatic mutations in cancer. Curr. Protoc. Hum. Genet. 91, 10.11.1–10.11.37 (2016). This publication describes COSMIC and provides protocols for access and data analysis.

    CAS  Google Scholar 

  11. Vogelstein, B. et al. Cancer genome landscapes. Science 339, 1546–1558 (2013). This review describes alterations to genes, and signalling and metabolic pathways driving cancer, identified through whole-genome sequencing of cancer samples.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Flaherty, K. T. et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809–819 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Yap, T. A., Sandhu, S. K., Carden, C. P. & de Bono, J. S. Poly(ADP-Ribose) polymerase (PARP) inhibitors: exploiting a synthetic lethal strategy in the clinic. CA Cancer J. Clin. 61, 31–49 (2011). This study describes the principles of PARP inhibitor-dependent synthetic lethality in BRCA-depleted cancers and its implications for cancer therapy.

    PubMed  Google Scholar 

  14. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).

    CAS  PubMed  Google Scholar 

  15. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011). This review describes an improved model of the hallmarks that define cancers and malignant transformation.

    CAS  PubMed  Google Scholar 

  16. Mertens, F., Johansson, B., Fioretos, T. & Mitelman, F. The emerging complexity of gene fusions in cancer. Nat. Rev. Cancer 15, 371–381 (2015).

    CAS  PubMed  Google Scholar 

  17. Cerveira, N. et al. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia 8, 826–832 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tian, E. et al. In multiple myeloma, 14q32 translocations are non-random chromosomal fusions driving high expression levels of the respective partner genes. Genes Chromosomes Cancer 53, 549–557 (2014).

    CAS  PubMed  Google Scholar 

  19. Zhao, X., Ghaffari, S., Lodish, H., Malashkevich, V. N. & Kim, P. S. Structure of the Bcr-Abl oncoprotein oligomerization domain. Nat. Struct. Biol. 9, 117–120 (2002).

    CAS  PubMed  Google Scholar 

  20. Nakata, T., Yokota, T., Emi, M. & Minami, S. Differential expression of multiple isoforms of the ELKS mRNAs involved in a papillary thyroid carcinoma. Genes Chromosomes Cancer 35, 30–37 (2002).

    CAS  PubMed  Google Scholar 

  21. Seong, K. M. et al. The histone acetyltransferase Myst2 regulates Nanog expression, and is involved in maintaining pluripotency and self-renewal of embryonic stem cells. FEBS Lett. 589, 941–950 (2015).

    Google Scholar 

  22. Sauer, T. et al. MYST2 acetyltransferase expression and histone H4 lysine acetylation are suppressed in AML. Exp. Hematol. 43, 794–802 (2015).

    CAS  PubMed  Google Scholar 

  23. Gerlinger, M. et al. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing. Nat. Genet. 46, 225–233 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Wellcome Sanger Institute. Gene view — KAT7. COSMIC https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=KAT7 (2018).

  25. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Awasthi, P., Foiani, M. & Kumar, A. ATM and ATR signaling at a glance. J. Cell Sci. 128, 4255–4262 (2015).

    CAS  PubMed  Google Scholar 

  27. Hilton, B. A. et al. ATR plays a direct antiapoptotic role at mitochondria which is regulated by prolyl isomerase Pin1. Mol. Cell 60, 35–46 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Wellcome Sanger Institute. Gene view — ATR. COSMIC https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ATR#tissue (2018).

  29. Knudson, A. G. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl Acad. Sci. USA 68, 820–823 (1971).

    PubMed  PubMed Central  Google Scholar 

  30. Adegbola, O. & Pasternack, G. R. Phosphorylated retinoblastoma protein complexes with pp32 and inhibits pp32-mediated apoptosis. J. Biol. Chem. 280, 15497–15502 (2005).

    CAS  PubMed  Google Scholar 

  31. Indovina, P., Pentimalli, F., Casini, N., Vocca, I. & Giordano, A. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy. Oncotarget 6, 17873–17890 (2015).

    PubMed  PubMed Central  Google Scholar 

  32. Agerbaek, M., Alsner, J., Marcussen, N., Lundbeck, F. & von der Maase, H. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer. Br. J. Cancer 89, 298–304 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Bid, H. K., Roberts, R. D., Manchanda, P. K. & Houghton, P. J. RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Mol. Cancer Ther. 12, 1925–1934 (2013).

    CAS  PubMed  Google Scholar 

  34. Singh, A. et al. Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformation. Oncogene 23, 9369–9380 (2004).

    CAS  PubMed  Google Scholar 

  35. Hofbauer, S. W. et al. Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells. Blood 123, 2181–2188 (2014).

    CAS  PubMed  Google Scholar 

  36. Deshmukh, J., Pofahl, R. & Haase, I. Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis. Cell Death Dis. 8, e2664 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Takiar, V., Ip, C. K. M., Gao, M., Mills, G. B. & Cheung, L. W. T. Neomorphic mutations create therapeutic challenges in cancer. Oncogene 36, 1607 (2016). This review describes the neomorphic mutations in cancer, including the best-known examples, and indicates potential therapeutic challenges associated with this class of mutations.

    PubMed  PubMed Central  Google Scholar 

  38. Hao, Y. et al. Gain of interaction with IRS1 by p110α helical domain mutants is crucial for their oncogenic functions. Cancer Cell 23, 583–593 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Pang, H. et al. Differential enhancement of breast cancer cell motility and metastasis by helical and kinase domain mutations of class IA PI3K. Cancer Res. 69, 8868–8876 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Dang, L. et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462, 739 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Gagné, M. L., Boulay, K., Topisirovic, I., Huot, M.-É. & Mallette, F. A. Oncogenic activities of IDH1/2 mutations: from epigenetics to cellular signaling. Trends Cell Biol. 27, 738–752 (2017).

    Google Scholar 

  42. Ward, P. S. et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzymatic activity that converts α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17, 225–234 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Turcan, S. et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483, 479–483 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Schneider, G., Schmidt-Supprian, M., Rad, R. & Saur, D. Tissue-specific tumorigenesis: context matters. Nat. Rev. Cancer 17, 239–253 (2017). This article presents a perspective on the molecular, cellular, systemic and environmental determinants of organ-specific tumorigenesis and the mechanisms of context-specific oncogenic signalling outputs.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Tremblay, C. S. et al. Loss-of-function mutations of dynamin 2 promote T-ALL by enhancing IL-7 signalling. Leukemia 30, 1993–2001 (2016).

    CAS  PubMed  Google Scholar 

  46. Xu, B. et al. The significance of dynamin 2 expression for prostate cancer progression, prognostication, and therapeutic targeting. Cancer Med. 3, 14–24 (2014).

    CAS  PubMed  Google Scholar 

  47. Razidlo, G. L. et al. Dynamin 2 potentiates invasive migration of pancreatic tumor cells through stabilization of the Rac1 GEF Vav1. Dev. Cell 24, 573–585 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Denli, A. M., Tops, B. B. J., Plasterk, R. H. A., Ketting, R. F. & Hannon, G. J. Processing of primary microRNAs by the microprocessor complex. Nature 432, 231–235 (2004).

    CAS  PubMed  Google Scholar 

  49. Torrezan, G. T. et al. Recurrent somatic mutation in DROSHA induces microRNA profile changes in Wilms tumour. Nat. Commun. 5, 4039 (2014). This work describes somatic mutations in the miRNA processing protein DROSHA, which drives cancer through genome-wide alteration of gene expression patterns.

    CAS  PubMed  Google Scholar 

  50. Rakheja, D. et al. Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumors. Nat. Commun. 2, 4802–4802 (2014).

    CAS  PubMed  Google Scholar 

  51. Czubak, K. et al. High copy number variation of cancer-related microRNA genes and frequent amplification of DICER1 and DROSHA in lung cancer. Oncotarget 6, 23399–23416 (2015).

    PubMed  PubMed Central  Google Scholar 

  52. Wellcome Sanger Institute. Hallmarks of Cancer — DROSHA. COSMIC https://cancer.sanger.ac.uk/cosmic/census-page/DROSHA (2018).

  53. Dwane, L., Gallagher, W. M., Ní Chonghaile, T. & O’Connor, D. P. The emerging role of non-traditional ubiquitination in oncogenic pathways. J. Biol. Chem. 292, 3543–3551 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Yamato, A. et al. Oncogenic activity of BIRC2 and BIRC3 mutants independent of nuclear factor-κB-activating potential. Cancer Sci. 106, 1137–1142 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Wang, D. et al. BIRC3 is a novel driver of therapeutic resistance in glioblastoma. Sci. Rep. 6, 21710 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Jeselsohn, R., Buchwalter, G., De Angelis, C., Brown, M. & Schiff, R. ESR1 mutations as a mechanism for acquired endocrine resistance in breast cancer. Nat. Rev. Clin. Oncol. 12, 573–583 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Liu, W. H. et al. MicroRNA-18a prevents estrogen receptor-alpha expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology 136, 683–693 (2009).

    CAS  PubMed  Google Scholar 

  58. Wu, X. et al. Nuclear TBLR1 as an ER corepressor promotes cell proliferation, migration and invasion in breast and ovarian cancer. Am. J. Cancer Res. 6, 2351–2360 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Daniels, G. et al. TBLR1 as an AR coactivator selectively activates AR target genes to inhibit prostate cancer growth. Endocr. Relat. Cancer 21, 127–142 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Cai, Y. et al. The NuRD complex cooperates with DNMTs to maintain silencing of key colorectal tumor suppressor genes. Oncogene 33, 2157–2168 (2014).

    CAS  PubMed  Google Scholar 

  61. O’Shaughnessy, A. & Hendrich, B. CHD4 in the DNA-damage response and cell cycle progression: not so NuRDy now. Biochem. Soc. Trans. 41, 777–782 (2013).

    PubMed  PubMed Central  Google Scholar 

  62. Benyoucef, A. et al. UTX inhibition as selective epigenetic therapy against TAL1-driven T cell acute lymphoblastic leukemia. Genes Dev. 30, 508–521 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Van der Meulen, J., Speleman, F. & Van Vlierberghe, P. The H3K27me3 demethylase UTX in normal development and disease. Epigenetics 9, 658–668 (2014).

    PubMed  PubMed Central  Google Scholar 

  64. Huang, H. et al. TET1 plays an essential oncogenic role in MLL-rearranged leukemia. Proc. Natl Acad. Sci. USA 110, 11994–11999 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Neri, F. et al. TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway. Oncogene 34, 4168 (2014).

    PubMed  Google Scholar 

  66. Godoy, A. S. et al. Altered corepressor SMRT expression and recruitment to target genes as a mechanism that change the response to androgens in prostate cancer progression. Biochem. Biophys. Res. Commun. 423, 564–570 (2012).

    CAS  PubMed  Google Scholar 

  67. Privalsky, M. L. The role of corepressors in transcriptional regulation by nuclear hormone receptors. Annu. Rev. Physiol. 66, 315–360 (2004).

    CAS  PubMed  Google Scholar 

  68. Blackmore, J. K. et al. The SMRT coregulator enhances growth of estrogen receptor-α-positive breast cancer cells by promotion of cell cycle progression and inhibition of apoptosis. Endocrinology 155, 3251–3261 (2014).

    PubMed  PubMed Central  Google Scholar 

  69. Yu, J., Li, Y., Ishizuka, T., Guenther, M. G. & Lazar, M. A. A. SANT motif in the SMRT corepressor interprets the histone code and promotes histone deacetylation. EMBO J. 22, 3403–3410 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Bhaskara, S. et al. Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell 18, 436–447 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Song, L. et al. Alteration of SMRT tumor suppressor function in transformed non-Hodgkin lymphomas. Cancer Res. 65, 4554–4561 (2005).

    CAS  PubMed  Google Scholar 

  72. Scafoglio, C., Smolka, M., Zhou, H., Perissi, V. & Rosenfeld, M. G. The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating the dynamics of checkpoint kinase 2 activation. PLOS ONE 8, e59986 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Manandhar, M., Boulware, K. S. & Wood, R. D. The ERCC1 and ERCC4 (XPF) genes and gene products. Gene 569, 153–161 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Emmert, S., Schneider, T. D., Khan, S. G. & Kraemer, K. H. The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms. Nucleic Acids Res. 29, 1443–1452 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Hartung, M. L. et al. H. pylori-induced DNA strand breaks are introduced by nucleotide excision repair endonucleases and promote NF-κB target gene expression. Cell Rep. 13, 70–79 (2015). This article describes how the infection of gastric epithelium cells by Helicobacter pylori may lead to generation of potentially oncogenic DNA double-strand breaks by nucleases normally involved in DNA repair.

    CAS  PubMed  Google Scholar 

  76. Le May, N., Fradin, D., Iltis, I., Bougnères, P. & Egly, J.-M. XPG and XPF endonucleases trigger chromatin looping and DNA demethylation for accurate expression of activated genes. Mol. Cell 47, 622–632 (2012).

    PubMed  Google Scholar 

  77. Bernardo, G. M. & Keri, R. A. FOXA1: a transcription factor with parallel functions in development and cancer. Biosci. Rep. 32, 113–130 (2012).

    CAS  PubMed  Google Scholar 

  78. Yamaguchi, N. et al. FoxA1 as a lineage-specific oncogene in luminal type breast cancer. Biochem. Biophys. Res. Commun. 365, 711–717 (2008).

    CAS  PubMed  Google Scholar 

  79. Grasso, C. S. et al. The mutational landscape of lethal castrate resistant prostate cancer. Nature 487, 239–243 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Jin, H.-J., Zhao, J. C., Ogden, I., Bergan, R. & Yu, J. Androgen receptor-independent function of FoxA1 in prostate cancer metastasis. Cancer Res. 73, 3725–3736 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Song, Y., Washington, M. K. & Crawford, H. C. Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer. Cancer Res. 70, 2115–2125 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Bernardo, G. M. et al. FOXA1 represses the molecular phenotype of basal breast cancer cells. Oncogene 32, 554–563 (2013).

    CAS  PubMed  Google Scholar 

  83. Zhan, T., Rindtorff, N. & Boutros, M. Wnt signaling in cancer. Oncogene 36, 1461–1473 (2017).

    CAS  PubMed  Google Scholar 

  84. Hanson, C. A. & Miller, J. R. Non-traditional roles for the adenomatous polyposis coli (APC) tumor suppressor protein. Gene 361, 1–12 (2005).

    CAS  PubMed  Google Scholar 

  85. Wellcome Sanger Institute. Gene view — APC. COSMIC https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=APC#tissue (2018).

  86. Nagata, S. Fas ligand-induced apoptosis. Annu. Rev. Genet. 33, 29–55 (1999).

    CAS  PubMed  Google Scholar 

  87. Yang, Y. et al. Fas signaling promotes gastric cancer metastasis through STAT3-dependent upregulation of fascin. PLOS ONE 10, e0125132 (2015).

    PubMed  PubMed Central  Google Scholar 

  88. Chen, L. et al. CD95/Fas promotes tumour growth. Nature 465, 492–496 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Ceppi, P. et al. CD95 and CD95L promote and protect cancer stem cells. Nat. Commun. 5, 5238–5238 (2014).

    CAS  PubMed  Google Scholar 

  90. Mullan, P. B., Quinn, J. E. & Harkin, D. P. The role of BRCA1 in transcriptional regulation and cell cycle control. Oncogene 25, 5854 (2006).

    CAS  PubMed  Google Scholar 

  91. Rodriguez, J. A., Au, W. W. Y. & Henderson, B. R. Cytoplasmic mislocalization of BRCA1 caused by cancer-associated mutations in the BRCT domain. Exp. Cell Res. 293, 14–21 (2004).

    CAS  PubMed  Google Scholar 

  92. Santivasi, W. L. et al. Association between cytosolic expression of BRCA1 and metastatic risk in breast cancer. Br. J. Cancer 113, 453–459 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Shimizu, Y. et al. BRCA1-IRIS overexpression promotes formation of aggressive breast cancers. PLOS ONE 7, e34102 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Chen, H. et al. Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma. Genes Cancer 6, 106–118 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Matsuura, S. et al. Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am. J. Med. Genet. A 140, 358–367 (2006).

    PubMed  Google Scholar 

  96. Kapanidou, M., Lee, S. & Bolanos-Garcia, V. M. BubR1 kinase: protection against aneuploidy and premature aging. Trends Mol. Med. 21, 364–372 (2015).

    CAS  PubMed  Google Scholar 

  97. Chao, C.-H. et al. DDX3, a DEAD box RNA helicase with tumor growth-suppressive property and transcriptional regulation activity of the p21waf1/cip1 promoter, is a candidate tumor suppressor. Cancer Res. 66, 6579–6588 (2006).

    CAS  PubMed  Google Scholar 

  98. Chen, H. H., Yu, H. I., Cho, W. C. & Tarn, W. Y. DDX3 modulates cell adhesion and motility and cancer cell metastasis via Rac1-mediated signaling pathway. Oncogene 34, 2790 (2014).

    PubMed  Google Scholar 

  99. Botlagunta, M. et al. Oncogenic role of DDX3 in breast cancer biogenesis. Oncogene 27, 3912–3922 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Gan, W. et al. SPOP promotes ubiquitination and degradation of the ERG oncoprotein to suppress prostate cancer progression. Mol. Cell 59, 917–930 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Zhao, W., Zhou, J., Deng, Z., Gao, Y. & Cheng, Y. SPOP promotes tumor progression via activation of beta-catenin/TCF4 complex in clear cell renal cell carcinoma. Int. J. Oncol. 49, 1001–1008 (2016).

    CAS  PubMed  Google Scholar 

  102. Delbridge, A. R. D., Valente, L. J. & Strasser, A. The role of the apoptotic machinery in tumor suppression. Cold Spring Harb. Perspect. Biol. 4, a008789 (2012).

    PubMed  PubMed Central  Google Scholar 

  103. Labi, V. & Erlacher, M. How cell death shapes cancer. Cell Death Dis. 6, e1675 (2015). This review describes the role of apoptosis as an anticancer defence mechanism but also as a process fuelling evolution of cancer and promoting the expansion of more aggressive subclones.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Pérez-Garijo, A. When dying is not the end: apoptotic caspases as drivers of proliferation. Semin. Cell Dev. Biol. https://doi.org/10.1016/j.semcdb.2017.11.036 (2017).

    Article  PubMed  Google Scholar 

  105. Bandopadhayay, P. et al. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat. Genet. 48, 273–282 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Steidl, C. et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature 471, 377–381 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Lin, A. et al. BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants. J. Neuropathol. Exp. Neurol. 71, 66–72 (2012).

    CAS  PubMed  Google Scholar 

  108. Wellcome Sanger Institute. Hallmarks of Cancer — PTEN. COSMIC https://cancer.sanger.ac.uk/cosmic/census-page/PTEN (2018).

Download references

Acknowledgements

The authors would like to thank J. Tate, who created the web pages presenting the functional descriptions of cancer genes. They also thank C. Rye, N. Bindal and C. Ramshaw as well as the COSMIC and Open Targets teams for testing and improving these pages. This work was supported by the Wellcome Trust (grant 206194) and by Open Targets (grant OTAR007).

Reviewer information

Nature Reviews Cancer thanks F. Ciccarelli, J. Korbel and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

Authors and Affiliations

Authors

Contributions

Z.S. researched data for the article, substantially contributed to the discussion of content and wrote, reviewed and edited the article. S.B., C.G.C. and S.A.W. researched data and reviewed and edited the article. I.D. substantially contributed to the discussion of content and reviewed and edited the article. S.A.F. substantially contributed to the discussion of content and wrote, reviewed and edited the article.

Corresponding author

Correspondence to Zbyslaw Sondka.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

COSMIC Cancer Gene Census: https://cancer.sanger.ac.uk/censusCOSMIC Database: https://cancer.sanger.ac.uk/cosmic

Glossary

Synthetic lethality

A mechanism using a combination of genetic and induced effects (for example, by a therapeutic agent) working together to induce cell death, where any single one of these effects is non-lethal.

Gain of function

A type of mutation resulting in an altered gene product with intensified activity or with a new biological function (neomorphic mutation).

Loss of function

A type of mutation resulting in an altered gene product with lower or no biological function.

Nucleotide excision repair

(NER). A DNA repair mechanism that removes DNA damage induced by ultraviolet light — mostly thymine dimers — and uses the complementary undamaged strand as a template to repair the damage.

Wilms tumour

Another name for nephroblastoma, a malignant embryonal neoplasm of the kidney.

Epithelial-to-mesenchymal transition

(EMT). A process in which epithelial cells lose cell polarity and cell–cell adhesion with accompanying increases in migratory and invasive capacities; EMT occurs during embryogenesis, fibrosis and wound healing but may also be an early event in cancer metastasis.

Anoikis

A form of programmed cell death triggered in anchorage-dependent cells by detachment of the cell from the extracellular matrix.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sondka, Z., Bamford, S., Cole, C.G. et al. The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. Nat Rev Cancer 18, 696–705 (2018). https://doi.org/10.1038/s41568-018-0060-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41568-018-0060-1

This article is cited by

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer