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.
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.
Authors: M Konishi; R Kikuchi-Yanoshita; K Tanaka; M Muraoka; A Onda; Y Okumura; N Kishi; T Iwama; T Mori; M Koike; K Ushio; M Chiba; S Nomizu; F Konishi; J Utsunomiya; M Miyaki Journal: Gastroenterology Date: 1996-08 Impact factor: 22.682
Authors: B Liu; R E Parsons; S R Hamilton; G M Petersen; H T Lynch; P Watson; S Markowitz; J K Willson; J Green; A de la Chapelle Journal: Cancer Res Date: 1994-09-01 Impact factor: 12.701
Authors: M Miyaki; M Konishi; R Kikuchi-Yanoshita; M Enomoto; T Igari; K Tanaka; M Muraoka; H Takahashi; Y Amada; M Fukayama Journal: Cancer Res Date: 1994-06-01 Impact factor: 12.701
Authors: R D Kolodner; N R Hall; J Lipford; M F Kane; M R Rao; P Morrison; L Wirth; P J Finan; J Burn; P Chapman Journal: Genomics Date: 1994-12 Impact factor: 5.736
Authors: L A Simms; G Radford-Smith; K G Biden; R Buttenshaw; M Cummings; J R Jass; J Young; S J Meltzer; B A Leggett Journal: Oncogene Date: 1998-10-15 Impact factor: 9.867
Authors: Asad Umar; C Richard Boland; Jonathan P Terdiman; Sapna Syngal; Albert de la Chapelle; Josef Rüschoff; Richard Fishel; Noralane M Lindor; Lawrence J Burgart; Richard Hamelin; Stanley R Hamilton; Robert A Hiatt; Jeremy Jass; Annika Lindblom; Henry T Lynch; Païvi Peltomaki; Scott D Ramsey; Miguel A Rodriguez-Bigas; Hans F A Vasen; Ernest T Hawk; J Carl Barrett; Andrew N Freedman; Sudhir Srivastava Journal: J Natl Cancer Inst Date: 2004-02-18 Impact factor: 13.506
Authors: Margreet Lüchtenborg; Matty P Weijenberg; Petra A Wark; A Merdan Saritas; Guido M J M Roemen; Goos N P van Muijen; Adriaan P de Bruïne; Piet A van den Brandt; Anton F P M de Goeij Journal: BMC Cancer Date: 2005-12-15 Impact factor: 4.430