Prevalence of somatic alterations in the colorectal cancer cell genome

TL Wang, C Rago, N Silliman, J Ptak… - Proceedings of the …, 2002 - National Acad Sciences
TL Wang, C Rago, N Silliman, J Ptak, S Markowitz, JKV Willson, G Parmigiani, KW Kinzler
Proceedings of the National Academy of Sciences, 2002National Acad Sciences
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 …
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.
National Acad Sciences