Prevalence of somatic alterations in the colorectal cancer cell genome

Tian Li Wang, Carlo Rago, Natalie Silliman, Janine Ptak, Sanford Markowitz, James K V Willson, Giovanni Parmigiani, Kenneth W. Kinzler, Bert Vogelstein, Victor E. Velculescu

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


Although a small fraction of human cancers have increased rates of somatic mutation because of known deficiencies in DNA repair, little is known about the prevalence of somatic alterations in the vast majority of human cancers. To systematically assess nonsynonymous somatic alterations in colorectal neoplasia, we used DNA sequencing to analyze ≈3.2 Mb of coding tumor DNA comprising 1,811 exons from 470 genes. In total, we identified only three distinct somatic mutations, comprising two missense changes and one 14-bp deletion, each in a different gene. The accumulation of approximately one nonsynonymous somatic change per Mb of tumor DNA is consistent with a rate of mutation in tumor cells that is similar to that of normal cells. These data suggest that most sporadic colorectal cancers do not display a mutator phenotype at the nucleotide level. They also have significant implications for the interpretation of somatic mutations in candidate tumor-suppressor genes.

Original languageEnglish (US)
Pages (from-to)3076-3080
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Mar 5 2002

ASJC Scopus subject areas

  • General


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