Mismatch repair deficiency leads to a unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity

ABSTRACT In order to determine the effects of mismatch repair (MMR) deficiencies in sporadic colorectal carcinomas, 45 such cancers were examined using a sensitive method called crypt

isolation technique. Loss of heterozygosity (LOH) in the MSH2 or MLH1 gene was more frequently observed in replication error (RER) (+) carcinomas than in RER (−) carcinomas, which implied

that loss of one normal allele could partly affect repair capacity. MSH2 gene defects at both alleles were observed in two carcinomas, which showed severe repair deficiencies. Interestingly,

unlike the situation observed in the p53 gene, the MSH2 and MLH1 genes did not show complete LOH. Novel crypt isolation-based subpopulation (CISP) analysis demonstrated that at least two

distinct carcinoma subpopulations existed in most carcinomas that showed incomplete LOH; one with and one without LOH. In one carcinoma that had germline mutation and somatic incomplete LOH

of the MSH2 gene, the mutator phenotype was only observed in populations affected in both alleles. Thus, the MSH2 gene appears to possess the two hits mechanism of tumor suppressor genes.

However, unlike the tumor suppressor genes, MMR gene defects lead to a unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity. Access through your institution

Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and

online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes

which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY

OTHERS MUTATIONAL LANDSCAPE OF NORMAL EPITHELIAL CELLS IN LYNCH SYNDROME PATIENTS Article Open access 17 May 2022 MUTATIONAL SIGNATURE SBS8 PREDOMINANTLY ARISES DUE TO LATE REPLICATION

ERRORS IN CANCER Article Open access 03 August 2020 MUTATIONAL SIGNATURES ASSOCIATION WITH REPLICATION TIMING IN NORMAL CELLS REVEALS SIMILARITIES AND DIFFERENCES WITH MATCHED CANCER TISSUES

Article Open access 15 May 2023 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Pathology, Central Clinical Laboratory, School of Medicine, Iwate Medical University, 19-1

Uchimaru, 020, Morioka, Japan Wataru Habano, Tamotsu Sugai & Shin-ichi Nakamura Authors * Wataru Habano View author publications You can also search for this author inPubMed Google

Scholar * Tamotsu Sugai View author publications You can also search for this author inPubMed Google Scholar * Shin-ichi Nakamura View author publications You can also search for this author

inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Habano, W., Sugai, T. & Nakamura, Si. Mismatch repair deficiency leads to a

unique mode of colorectal tumorigenesis characterized by intratumoral heterogeneity. _Oncogene_ 16, 1259–1265 (1998). https://doi.org/10.1038/sj.onc.1201651 Download citation * Received: 10

July 1997 * Revised: 15 October 1997 * Accepted: 15 October 1997 * Published: 19 March 1998 * Issue Date: 12 March 1998 * DOI: https://doi.org/10.1038/sj.onc.1201651 SHARE THIS ARTICLE

Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided

by the Springer Nature SharedIt content-sharing initiative KEYWORDS * mismatch repair gene * intratumoral heterogeneity * subpopulation analysis