Allelic losses and DNA methylation at DNA mismatch repair loci in sporadic colorectal cancer

被引：16

作者：

Benachenhou, N

Guiral, S

Gorska-Flipot, I

Michalski, R

Labuda, D

Sinnett, D

机构：

[1] Hop St Justine, Res Ctr, Charles Bruneau Canc Ctr, Div Hematooncol, Montreal, PQ H3T 1C5, Canada

[2] Univ Montreal, Montreal Hotel Dieu Hosp, Div Pathol, Quebec City, PQ, Canada

[3] Victoria Hosp, Dept Pathol, Quebec City, PQ, Canada

[4] Univ Montreal, Dept Pediat, Quebec City, PQ, Canada

来源：

CARCINOGENESIS | 1998年 / 19卷 / 11期

关键词：

D O I：

10.1093/carcin/19.11.1925

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Normal and tumor DNA samples of 35 patients with sporadic colorectal carcinoma were analyzed for microsatellite alterations at 12 markers linked to mismatch repair loci: hMLH1, hMSH2, hMSH3, hMSH6, hPMS1 and hPMS2. Remarkably, no correlation was observed between the replication error phenotype (RER+) and allelic losses at these loci. Hemizygous deletions, seen in 6/35 (17%) informative cases at hMLH1, 4/27 (15 %) at hMSH2/hMSH6 and 6/34 (18%) at hMSH3, were rarely found in RER+ tumors. Since mismatch repair protein components act in molecular complexes of defined stoichiometry we propose that hemizygous deletion of the corresponding loci may be involved in colorectal tumorigenesis through defects in cellular functions other than replication error correction. The analysis of the methylation status of the promoter region of hMLH(1) revealed that methylation might be an important mechanism of this locus inactivation in RER+ sporadic colorectal cancer.

引用

页码：1925 / 1929

页数：5

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