Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters : A study of the TGFβRII, BAX, HMSH3, HMSH6, IGFIIR and BLM genes

Colon carcinomas with microsatellite mutator phenotype exhibit specific genetic and clinico-pathological features. This report describes the analysis of 63 "microsatellite instability-high" (MSI-H) tumors for the presence of mutations in microsatellites located in the coding regions (CDRs)...

Full description

Saved in:
Bibliographic Details
Published in:International journal of cancer 2000-05, Vol.89 (3), p.230-235
Main Authors: CALIN, G. A, GAFA, R, TIBILETTI, M. G, HERLEA, V, BECHEANU, G, CAVAZZINI, L, BARBANTI-BRODANO, G, NENCI, I, NEGRINI, M, LANZA, G
Format: Article
Language:English
Subjects:
Biological and medical sciences
BLM gene
Gastroenterology. Liver. Pancreas. Abdomen
Medical sciences
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Colon carcinomas with microsatellite mutator phenotype exhibit specific genetic and clinico-pathological features. This report describes the analysis of 63 "microsatellite instability-high" (MSI-H) tumors for the presence of mutations in microsatellites located in the coding regions (CDRs) of 6 genes: TGF beta RII, BAX, hMSH3, hMSH6, IGFIIR, and BLM. The following frequencies of mutations were detected: TGF beta RII (70%), BAX (54%), hMSH3 (36.5%), IGFIIR (22%), hMSH6 (17.5%), and BLM (16%). The overall picture revealed combinations of mutations suggestive of a progressive order of accumulation, with mutations of TGF beta RII and BAX first, followed by frame-shifts in hMSH3, hMSH6, IGFIIR, and BLM. Correlations with 12 clinico-pathological parameters revealed that tumors with frameshifts in 1 or 2 CDRs were significantly better differentiated than tumors with frameshifts in more than 2 CDRs. We also found that mutations in the hMSH3 gene were significantly associated with decreased wall invasiveness and aneuploidy, and frameshifts in the BLM gene were significantly associated with the mucinous histotype. A trend toward an association between hMSH3 and IGFIIR with the medullary and conventional adenocarcinoma histotypes, respectively, was seen. Our results strengthen the concept that mutations in target genes have a role in the tumorigenic process of MSI-H tumors, and indicate that frameshifts in microsatellites located in CDRs occur in a limited number of combinations that could determine distinct clinico-pathological traits.
ISSN:0020-7136
1097-0215
DOI:10.1002/1097-0215(20000520)89:3<230::AID-IJC4>3.0.CO;2-J