Genomic Loci Susceptible to Replication Errors in Cancer Cells

Overview

Journal Br J Cancer

Specialty Oncology

Date 1998 Oct 29

PMID 9792139

Citations 6

Authors

M Krajinovic

C Richer

I Gorska-Flipot

L Gaboury

I Novakovic

D Labuda

D Sinnett

Affiliations

Soon will be listed here.

Abstract

Microsatellite instability due to a deficiency in DNA mismatch repair is characteristic of a replication error (RER) phenotype. This widespread genomic instability is well documented in hereditary non-polyposis colon cancer (HNPCC) as well as subsets of sporadic carcinomas. Features of the RER phenotype such as the early appearance in tumour development and better prognosis of RER+ colorectal tumours render its examination important for cancer patients. Recently, we identified four loci that were shown to be highly susceptible to RER in cancer cells. Here, we used these loci to detect the RER phenotype in sporadic carcinomas of colon, breast, lung, endometrium and ovary. Replication errors revealed by these four markers followed the same tumour specificity as observed in HNPCC patients. In particular, 24% (6/25) of colorectal, 33% (4/12) of endometrial and 17% (2/12) of ovarian cancers displayed the RER phenotype characterized by an increased allelic mobility, whereas none of the breast (n = 22) and the lung (n = 27) carcinomas were found to be unstable. Assaying RERs sensitive loci provides us with a useful diagnostic tool for HNPCC-like sporadic tumours.

Citing Articles

Frequency of mismatch repair deficiency in ovarian cancer: a systematic review This article is a US Government work and, as such, is in the public domain of the United States of America.

Murphy M, Wentzensen N Int J Cancer. 2010; 129(8):1914-22.

PMID: 21140452 PMC: 3107885. DOI: 10.1002/ijc.25835.

Application of molecular diagnostics for the detection of Lynch syndrome.

Pino M, Chung D Expert Rev Mol Diagn. 2010; 10(5):651-65.

PMID: 20629513 PMC: 2929365. DOI: 10.1586/erm.10.45.

Systematic review and meta-analysis of ovarian cancers: estimation of microsatellite-high frequency and characterization of mismatch repair deficient tumor histology.

Pal T, Permuth-Wey J, Kumar A, Sellers T Clin Cancer Res. 2008; 14(21):6847-54.

PMID: 18980979 PMC: 2655731. DOI: 10.1158/1078-0432.CCR-08-1387.

Loss of DNA mismatch repair protein hMSH6 in ovarian cancer is histotype-specific.

Zhai Q, Rosen D, Lu K, Liu J Int J Clin Exp Pathol. 2008; 1(6):502-9.

PMID: 18787632 PMC: 2480583.

A review of the clinical relevance of mismatch-repair deficiency in ovarian cancer.

Pal T, Permuth-Wey J, Sellers T Cancer. 2008; 113(4):733-42.

PMID: 18543306 PMC: 2644411. DOI: 10.1002/cncr.23601.

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