TY - JOUR
T1 - APC mutations in colorectal tumors with mismatch repair deficiency
AU - Huang, Jian
AU - Papadopoulos, Nickolas
AU - Mckinley, Aileen J.
AU - Farrington, Susan M.
AU - Curtis, Lucy J.
AU - Wyllie, Andrew H.
AU - Zheng, Shu
AU - Willson, James K.V.
AU - Markowitz, Sanford D.
AU - Morin, Pat
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
AU - Dunlop, Malcolm G.
PY - 1996/8/20
Y1 - 1996/8/20
N2 - We have investigated the influence of genetic instability [replication error (RER) phenotype) on APC (adenomatous polyposis coli), a gene thought to initiate colorectal tumorigenesis. The prevalence of APC mutations was similar in RER and non-RER tumors, indicating that both tumor types share this step in neoplastic transformation. However, in a total of 101 sequenced mutations, we noted a substantial excess of APC frameshift mutations in the RER cases (70% in RER tumors versus 47% in non-RER tumors, P < 0.04). These frameshifts were characteristic of mutations arising in cells deficient in DNA mismatch repair, with a predilection for mononucleotide repeats in the RER tumors (P < 0.0002), particularly (A)(n) tracts (P < 0.00007). These findings suggest that the genetic instability that is reflected by the RER phenotype precedes, and is responsible for, APC mutation in RER large bowel tumors and have important implications for understanding the very earliest stages of neoplasia in patients with tumors deficient in mismatch repair.
AB - We have investigated the influence of genetic instability [replication error (RER) phenotype) on APC (adenomatous polyposis coli), a gene thought to initiate colorectal tumorigenesis. The prevalence of APC mutations was similar in RER and non-RER tumors, indicating that both tumor types share this step in neoplastic transformation. However, in a total of 101 sequenced mutations, we noted a substantial excess of APC frameshift mutations in the RER cases (70% in RER tumors versus 47% in non-RER tumors, P < 0.04). These frameshifts were characteristic of mutations arising in cells deficient in DNA mismatch repair, with a predilection for mononucleotide repeats in the RER tumors (P < 0.0002), particularly (A)(n) tracts (P < 0.00007). These findings suggest that the genetic instability that is reflected by the RER phenotype precedes, and is responsible for, APC mutation in RER large bowel tumors and have important implications for understanding the very earliest stages of neoplasia in patients with tumors deficient in mismatch repair.
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U2 - 10.1073/pnas.93.17.9049
DO - 10.1073/pnas.93.17.9049
M3 - Article
C2 - 8799152
AN - SCOPUS:0010945939
SN - 0027-8424
VL - 93
SP - 9049
EP - 9054
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 - 17
ER -