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Nature DOI:10.1038/nature12912

Discovery and saturation analysis of cancer genes across 21 tumour types.

Publication TypeJournal Article
Year of Publication2014
AuthorsLawrence, MS, Stojanov, P, Mermel, CH, Robinson, JT, Garraway, LA, Golub, TR, Meyerson, M, Gabriel, SB, Lander, ES, Getz, G
Date Published2014 Jan 23
KeywordsApoptosis, Case-Control Studies, Cell Proliferation, Chromatin, DNA Mutational Analysis, Exome, Genes, Neoplasm, Genome, Human, Genomic Instability, Genomics, Humans, Immune Evasion, Mutation Rate, Neoplasms, Point Mutation, RNA Processing, Post-Transcriptional, Sample Size

Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600-5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics.


Alternate JournalNature
PubMed ID24390350
PubMed Central IDPMC4048962
Grant ListR01 CA157304 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States