TY - JOUR
T1 - Prevalence of somatic alterations in the colorectal cancer cell genome
AU - Wang, Tian Li
AU - Rago, Carlo
AU - Silliman, Natalie
AU - Ptak, Janine
AU - Markowitz, Sanford
AU - Willson, James K.V.
AU - Parmigiani, Giovanni
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
AU - Velculescu, Victor E.
PY - 2002/3/5
Y1 - 2002/3/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=18344378411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18344378411&partnerID=8YFLogxK
U2 - 10.1073/pnas.261714699
DO - 10.1073/pnas.261714699
M3 - Article
C2 - 11867767
AN - SCOPUS:18344378411
SN - 0027-8424
VL - 99
SP - 3076
EP - 3080
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -