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Genomics

Combing the genome for cancer genes

Nature Reviews Cancer volume 7, page 891 (2007)Cite this article

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Vogelstein and colleagues sequenced all the genes in the Reference Sequence database (a consolidated collection consisting of most human gene sequences) from 11 breast and 11 colorectal tumours. Of the 18,191 genes they sequenced, 1,718 had a non-silent mutation in at least one tumour sample. However, most of these are likely to be passenger mutations — ones that are not causally involved in tumorigenesis but which have arisen in clones that subsequently acquired causal mutations. The authors used a two-stage design that included investigation of 24 to 120 additional tumour samples to help identify genes that are most likely to be causal. By this method, they identified 280 candidate cancer genes.

In addition to analysing these candidates on a gene-by-gene basis, the authors classified them into pathways. Mutations affecting the phosphatidylinositol 3-kinase (PI3K) pathway were particularly common although, interestingly, different parts of the pathway were mutated in breast and colorectal tumours. The overall picture of the genomic landscape of cancer that emerged from this study was that, although there may be some genes that are mutated in many tumours (such as TP53 ), most of the candidate cancer genes were mutated at relatively low frequencies — typically in fewer than 5% of tumours.

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ORIGINAL RESEARCH PAPERS

  1. Wood, L. D. et al. The genomic landscapes of human breast and colorectal cancers. Science 11 October 2007 (doi:10.1126/science.1145720)

  2. Weir, B. A. et al. Characterizing the cancer genome in lung adenocarcinoma. Nature 4 November 2007 (doi:10.1038/nature06358)

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Authors
  1. Patrick Goymer
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Goymer, P. Combing the genome for cancer genes. Nat Rev Cancer 7, 891 (2007). https://doi.org/10.1038/nrc2279

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  • DOI: https://doi.org/10.1038/nrc2279

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