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Discovery and saturation analysis of cancer genes across 21 tumour types

Author

Listed:
  • Michael S. Lawrence

    (Broad Institute of MIT and Harvard, 7 Cambridge Center)

  • Petar Stojanov

    (Broad Institute of MIT and Harvard, 7 Cambridge Center
    Dana-Farber Cancer Institute, 450 Brookline Avenue)

  • Craig H. Mermel

    (Broad Institute of MIT and Harvard, 7 Cambridge Center
    Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA)

  • James T. Robinson

    (Broad Institute of MIT and Harvard, 7 Cambridge Center)

  • Levi A. Garraway

    (Broad Institute of MIT and Harvard, 7 Cambridge Center
    Dana-Farber Cancer Institute, 450 Brookline Avenue
    Harvard Medical School, 25 Shattuck Street)

  • Todd R. Golub

    (Broad Institute of MIT and Harvard, 7 Cambridge Center
    Dana-Farber Cancer Institute, 450 Brookline Avenue
    Harvard Medical School, 25 Shattuck Street
    Howard Hughes Medical Institute, 4000 Jones Bridge Road)

  • Matthew Meyerson

    (Broad Institute of MIT and Harvard, 7 Cambridge Center
    Dana-Farber Cancer Institute, 450 Brookline Avenue
    Harvard Medical School, 25 Shattuck Street)

  • Stacey B. Gabriel

    (Broad Institute of MIT and Harvard, 7 Cambridge Center)

  • Eric S. Lander

    (Broad Institute of MIT and Harvard, 7 Cambridge Center
    Harvard Medical School, 25 Shattuck Street
    Massachusetts Institute of Technology, 77 Massachusetts Avenue)

  • Gad Getz

    (Broad Institute of MIT and Harvard, 7 Cambridge Center
    Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA
    Harvard Medical School, 25 Shattuck Street)

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.

Suggested Citation

  • Michael S. Lawrence & Petar Stojanov & Craig H. Mermel & James T. Robinson & Levi A. Garraway & Todd R. Golub & Matthew Meyerson & Stacey B. Gabriel & Eric S. Lander & Gad Getz, 2014. "Discovery and saturation analysis of cancer genes across 21 tumour types," Nature, Nature, vol. 505(7484), pages 495-501, January.
    • Handle: RePEc:nat:nature:v:505:y:2014:i:7484:d:10.1038_nature12912
    DOI: 10.1038/nature12912
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