APC mutations in colorectal tumors with mismatch repair deficiency Export

@article{citeulike:1272132, abstract = {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 ofAPC 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 ofAPC 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). 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.}, author = {Huang, J. I. A. N. and Papadopoulos, Nickolas and Mckinley, Aileen J. and Farrington, Susan M. and Curtisi, Lucy J. and Wylliet, Andrew H. and Zhengii, S. H. U. and Willson, James K. V. and Markowitz, Sanford D. and Morin, P. A. T. and Kinzler, Kenneth W. and Vogelstein, B. E. R. T. and Dunlop, Malcolm G.}, citeulike-article-id = {1272132}, journal = {Proc. Natl. Acad. Sci.}, keywords = {apc, cancer, colorectal}, posted-at = {2007-05-02 15:54:23}, priority = {2}, title = {APC mutations in colorectal tumors with mismatch repair deficiency} }

TY - JOUR ID - citeulike:1272132 L3 - citeulike-article-id:1272132 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 ofAPC 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 ofAPC 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). 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. JF - Proc. Natl. Acad. Sci. TI - APC mutations in colorectal tumors with mismatch repair deficiency KW - apc KW - cancer KW - colorectal AU - Huang, JIAN AU - Papadopoulos, Nickolas AU - Mckinley, Aileen AU - Farrington, Susan AU - Curtisi, Lucy AU - Wylliet, Andrew AU - Zhengii, SHU AU - Willson, James AU - Markowitz, Sanford AU - Morin, PAT AU - Kinzler, Kenneth AU - Vogelstein, BERT AU - Dunlop, Malcolm ER -