Premium
Genetic progression in microsatellite instability high (MSI‐H) colon cancers correlates with clinico‐pathological parameters: A study of the TGRβRII , BAX , hMSH3 , hMSH6 , IGFIIR and BLM genes
Author(s) -
Calin George A.,
Gafà Roberta,
Tibiletti Maria G.,
Herlea Vlad,
Becheanu Gabriel,
Cavazzini Luigi,
BarbantiBrodano Giuseppe,
Nenci Italo,
Negrini Massimo,
Lanza Giovanni
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000520)89:3<230::aid-ijc4>3.0.co;2-j
Subject(s) - microsatellite instability , biology , dna mismatch repair , adenocarcinoma , microsatellite , cancer research , mutation , gene , genetics , cancer , dna repair , allele
Abstract 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: TGFβRII , BAX , hMSH3 , hMSH6 , IGFIIR , and BLM . The following frequencies of mutations were detected: TGFβRII (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 TGFβRII and BAX first, followed by frameshifts 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. Int. J. Cancer 89:230–235, 2000. © 2000 Wiley‐Liss, Inc.