✦ LIBER ✦

Methylation pattern of different regions of the MLH1 promoter and silencing of gene expression in hereditary and sporadic colorectal cancer

✍ Scribed by Mirco Menigatti; Carmela Di Gregorio; Francesca Borghi; Elisa Sala; Alessandra Scarselli; Monica Pedroni; Moira Foroni; Piero Benatti; Luca Roncucci; Maurizio Ponz de Leon; Antonio Percesepe

Publisher: John Wiley and Sons
Year: 2001
Tongue: English
Weight: 141 KB
Volume: 31
Category: Article
ISSN: 1045-2257
DOI: 10.1002/gcc.1154

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Nonrandom, widespread promoter methylation of tumor suppressor genes is a common mechanism of gene inactivation during tumorigenesis. We examined the methylation status of two distinct regions of the MLH1 promoter (proximal and distal to the transcription start site) and the MLH1 gene expression by methylation‐specific PCR and immunohistochemistry. A total of 72 colorectal tumors, both with (n = 51, 22 affected by hereditary nonpolyposis colorectal cancer, HNPCC, defined according to the international clinical criteria and 29 sporadic cases) and without microsatellite instability (MSI) (n = 21) were studied. Methylation was present in at least one of the two promoter regions in 86% of the sporadic MSI cases, in 33% of the cases lacking MSI, and in 23% of the HNPCC tumors. In the HNPCC cases with a known MLH1 mutation (n = 10) none of the two promoter regions was methylated. Hypermethylation in both MLH1 promoter regions was seen in 45% of the MSI sporadic cases vs. 5% of the MSI‐negative cases and 0% of the HNPCC cases. The overall concordance between the two promoter regions regarding methylation status was good (P = 0.009), but no significant correlation between methylation and suppression of the MLH1 immunohistochemical expression was found. Our data confirm that mutation and hypermethylation are mutually exclusive mechanisms in inducing mismatch repair deficiency and support the hypothesis of methylation as a process evenly distributed along the different regions of the promoter. © 2001 Wiley‐Liss, Inc.

📜 SIMILAR VOLUMES

Methylation profile of the MLH1 promoter

Methylation profile of the MLH1 promoter region and their relationship to colorectal carcinogenesis

✍ Yasuyuki Miyakura; Kokichi Sugano; Fumio Konishi; Noriko Fukayama; Seiji Igarash 📂 Article 📅 2002 🏛 John Wiley and Sons 🌐 English ⚖ 438 KB

## Abstract Methylation of the __MLH1__ promoter region has been suggested to be a principal mechanism of gene inactivation in sporadic microsatellite instability (MSI)–positive colorectal carcinoma. Recently, we have shown a novel methylation profile of the __MLH1__ promoter region (i.e., full, pa

Hereditary nonpolyposis colorectal cance

Hereditary nonpolyposis colorectal cancer: Frequent occurrence of large genomic deletions in MSH2 and MLH1 genes

✍ Yaping Wang; Waltraut Friedl; Christof Lamberti; Matthias Jungck; Micaela Mathia 📂 Article 📅 2002 🏛 John Wiley and Sons 🌐 French ⚖ 190 KB 👁 1 views

## Abstract Hereditary nonpolyposis colorectal cancer (HNPCC) is often caused by a deficiency in DNA mismatch repair. By using conventional methods of mutation analysis, point mutations in the DNA mismatch repair genes __MSH2__ and __MLH1__ have been detected in up to 64% of patients suspected of H

High-resolution methylation analysis of

High-resolution methylation analysis of the hMLH1 promoter in sporadic endometrial and colorectal carcinomas

✍ Maria Strazzullo; Antonio Cossu; Paola Baldinu; Maria Colombino; Maria P. Satta; 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 157 KB 👁 2 views

## Abstract ## BACKGROUND Microsatellite instability (MSI) has been reported in endometrial carcinoma (EC) and in colorectal carcinoma (CRC), primarily as a result of defective DNA mismatch repair (MMR). The MMR gene __hMLH1__ commonly is inactivated in both EC and CRC. In the current study, epige

Mutation sharing, predominant involvemen

Mutation sharing, predominant involvement of the MLH1 gene and description of four novel mutations in hereditary nonpolyposis colorectal cancer

✍ Mari Holmberg; Paula Kristo; Robert B. Chadwicks; Jukka-Pekka Mecklin; Heikki Jä 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 37 KB 👁 2 views

Worldwide, the DNA mismatch repair genes MSH2 and MLH1 account for a major share and almost equal proportions of hereditary nonpolyposis colorectal cancer (HNPCC). Furthermore, the predisposing mutation usually varies from kindred to kindred. In this study, we screened 29 verified or putative HNPCC

A specific CpG methylation pattern of th

A specific CpG methylation pattern of the MGMT promoter region associated with reduced MGMT expression in primary colorectal cancers

✍ Klaus K.-F. Herfarth; Thomas P. Brent; Rebecca P. Danam; Joanna S. Remack; Ira J 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 122 KB 👁 2 views

The enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) protects cells from the cytotoxic and mutagenic effects of alkylating agents. Approximately 20% of tumor cell lines lack MGMT activity and are highly sensitive to alkylating agents. In established cancer cell lines, MGMT expression appears t

−160C/A polymorphism in the E-cadherin g

−160C/A polymorphism in the E-cadherin gene promoter and risk of hereditary, familial and sporadic prostate cancer

✍ Björn-Anders Jonsson; Hans-Olov Adami; Maria Hägglund; Anders Bergh; Ingela Göra 📂 Article 📅 2004 🏛 John Wiley and Sons 🌐 French ⚖ 167 KB 👁 2 views

## Abstract The __E‐cadherin__ (__CDH1__) gene has been associated with prostate carcinogenesis. The C/A polymorphism −160 base pairs relative to the transcription start site has been shown to decrease gene transcription. We analyzed the association between this polymorphism and the risk of sporadi