| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Surgery, Jichi Medical School, 3311-1 Yakushiji, Minamikawachimachi, Tochigi 324-0498, Japan
2 Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome Bunkyo-ku, Tokyo 113-8697, Japan
3 Department of Pharmacology, Kitasato University, 5-9-1 Shirogane, Minato-ku, Tokyo 108-8641, Japan
Dr Shitoh kshitoh{at}jichi.ac.jp Aims—Microsatellite instability (MSI) was first observed in hereditary non-polyposis colorectal carcinoma (HNPCC) and was subsequently seen in non-familial colorectal carcinoma. The relation between MSI and cancer associated genes in non-familial colorectal carcinomas has yet to be evaluated. To clarify this matter, changes in cancer associated genes were examined in non-familial colorectal carcinomas.
Methods—Alterations in the adenomatous polyposis coli (APC), p53, and Ki-ras genes were analysed in 24 MSI high (alterations in four to seven of seven loci), nine MSI low (alterations in one to three of seven loci), and 31 MSI negative non-familial carcinomas. The hMSH2 and hMLH1 genes were also analysed in 24 MSI high carcinomas.
Results—Both the frequencies and types of alterations in the APC and p53 genes in MSI high carcinomas were the same as those in MSI low and MSI negative carcinomas; however, they were different from those seen in HNPCC. The frequency of Ki-ras mutation was significantly lower in the MSI high cases (two of 24; 8%) than in the others (15 of 38; 39%). Somatic mutation of hMSH2 or hMLH1 was detected in six of 24 (25%) of the MSI high cases.
Conclusions—These results suggest that APC and p53 alterations occur irrespective of microsatellite instability status in non-familial colorectal carcinomas, and that Ki-ras mutation is not involved in MSI high non-familial colorectal carcinoma. The pathogenesis of these carcinomas may differ from both the usual adenoma–carcinoma sequence and HNPCC carcinogenesis.
Key Words: microsatellite instability • non-familial colorectal carcinoma • cancer associated genes
This article has been cited by other articles:
|
|
 |
|
  J R Jass and J Behrens Wnt pathway may not be implicated in all routes to colorectal cancer * Author's reply Gut, February 1, 2007; 56(2): 309 - 310. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bacani, R. Zwingerman, N. Di Nicola, S. Spencer, T. Wegrynowski, K. Mitchell, K. Hay, M. Redston, E. Holowaty, D. Huntsman, et al. Tumor Microsatellite Instability in Early Onset Gastric Cancer J. Mol. Diagn., October 1, 2005; 7(4): 465 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Oliveira, J. L. Westra, D. Arango, M. Ollikainen, E. Domingo, A. Ferreira, S. Velho, R. Niessen, K. Lagerstedt, P. Alhopuro, et al. Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status Hum. Mol. Genet., October 1, 2004; 13(19): 2303 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Luchtenborg, M. P. Weijenberg, G. M. J. M. Roemen, A. P. de Bruine, P. A. van den Brandt, M. H. F. M. Lentjes, M. Brink, M. van Engeland, R. A. Goldbohm, and A. F. P. M. de Goeij APC mutations in sporadic colorectal carcinomas from The Netherlands Cohort Study Carcinogenesis, July 1, 2004; 25(7): 1219 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Umar, C. R. Boland, J. P. Terdiman, S. Syngal, A. d. l. Chapelle, J. Ruschoff, R. Fishel, N. M. Lindor, L. J. Burgart, R. Hamelin, et al. Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability J Natl Cancer Inst, February 18, 2004; 96(4): 261 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Plawski, J Lubinski, T Banasiewicz, J Paszkowski, D Lipinski, A Strembalska, G Kurzawski, T Byrski, S Zajaczek, D Hodorowicz-Zaniewska, et al. Novel germline mutations in the adenomatous polyposis coli gene in Polish families with familial adenomatous polyposis J. Med. Genet., January 1, 2004; 41(1): e11 - 11. [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Lindor, L. J. Burgart, O. Leontovich, R. M. Goldberg, J. M. Cunningham, D. J. Sargent, C. Walsh-Vockley, G. M. Petersen, M. D. Walsh, B. A. Leggett, et al. Immunohistochemistry Versus Microsatellite Instability Testing in Phenotyping Colorectal Tumors J. Clin. Oncol., February 15, 2002; 20(4): 1043 - 1048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J R Jass, K Shitoh, F Konishi, T Furukawa, H Nagai, M Miyaki, T Iijima, and T Tsukamoto Microsatellite unstable colorectal cancer J. Clin. Pathol., July 1, 2001; 54(7): 573 - 574. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhang, J. Yu, J. K. V. Willson, S. D. Markowitz, K. W. Kinzler, and B. Vogelstein Short Mononucleotide Repeat Sequence Variability in Mismatch Repair-deficient Cancers Cancer Res., May 1, 2001; 61(9): 3801 - 3805. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
| Journal of Clinical Pathology | Molecular Pathology |
