title: Discovery and saturation analysis of cancer genes across 21 tumour types.
abstract: 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.
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lawrence
authors.affiliation: 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Petar
authors.initials: P
authors.lastname: Stojanov
authors.affiliation: 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital, Cancer Center and Department of Pathology, 55 Fruit Street, Boston, Massachusetts 02114, USA.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Mermel
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Robinson
authors.affiliation: 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.affiliation: 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [4] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.affiliation: 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.affiliation: 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [3] Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [4].
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.affiliation: 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital, Cancer Center and Department of Pathology, 55 Fruit Street, Boston, Massachusetts 02114, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [4].
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
mesh_terms: D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D023281:Genomics; D006801:Humans; D057131:Immune Evasion / Q000235:genetics; D059645:Mutation Rate; D009369:Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D018401:Sample Size
chemical_list: D002843:Chromatin