Cancer Res. 2002 Jul 15;62(14):3925-8.

A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor.

Gazzoli I, Loda M, Garber J, Syngal S, Kolodner RD.

Source

Ludwig Institute of Cancer Research, University of California San Diego School of Medicine, La Jolla, California 92093, USA. igazzoli@ucsd.edu

Abstract

Fourteen suspected hereditary nonpolyposis colorectal carcinoma cases with microsatellite unstable(microsatellite instability-high; MSI-H) tumors but no germ-line MSH2, MSH6, or MLH1 mutations were examined for hypermethylation of CpG sites in the critical promoter region of MLH1. The methylation patterns were determined using methylation-specific PCR and by sequence analysis of sodium bisulfite-treated genomic DNA. In one case, DNA hypermethylation of one allele was detected in DNA isolated from blood. In the MSI-H tumor from this case, the unmethylated MLH1 allele was eliminated by loss of heterozygosity, and the methylated allele was retained. This biallelic inactivation resulted in loss of expression of MLH1 in the tumor as confirmed by immunohistochemistry. These results suggest a novel mode of germ-line inactivation of a cancer susceptibility gene.

PMID:: 12124320; [PubMed - indexed for MEDLINE]

Free full text

LinkOut - more resources

Full Text Sources

HighWire Press

Other Literature Sources

Medical

MLH1 Gene - Genetics Home Reference

Supplemental Content

Save items

Related citations in PubMed

Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR. [Clin Cancer Res. 2007]
Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR.
Bettstetter M, Dechant S, Ruemmele P, Grabowski M, Keller G, Holinski-Feder E, Hartmann A, Hofstaedter F, Dietmaier W. Clin Cancer Res. 2007 Jun 1; 13(11):3221-8.
Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. [Am J Pathol. 2000]
Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers.
Kuismanen SA, Holmberg MT, Salovaara R, de la Chapelle A, Peltomäki P. Am J Pathol. 2000 May; 156(5):1773-9.
The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers. [Br J Cancer. 2005]
The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers.
Lawes DA, Pearson T, Sengupta S, Boulos PB. Br J Cancer. 2005 Aug 22; 93(4):472-7.
Review [Germ-line epimutations and human cancer]. [Ai Zheng. 2009]
Review [Germ-line epimutations and human cancer].
Wu PY, Fan YM, Wang YP. Ai Zheng. 2009 Dec; 28(12):1236-42.
Review Molecular tumor clocks and dynamic phenotype. [Am J Pathol. 1997]
Review Molecular tumor clocks and dynamic phenotype.
Shibata D. Am J Pathol. 1997 Sep; 151(3):643-6.

See reviews... See all...

Cited by 25 PubMed Central articles

Germline promoter hypermethylation of tumor suppressor genes in gastric cancer. [World J Gastroenterol. 2012]
Germline promoter hypermethylation of tumor suppressor genes in gastric cancer.
Wu PY, Zhang Z, Wang JM, Guo WW, Xiao N, He Q, Wang YP, Fan YM. World J Gastroenterol. 2012 Jan 7; 18(1):70-8.
Review Epigenetic changes of DNA repair genes in cancer. [J Mol Cell Biol. 2011]
Review Epigenetic changes of DNA repair genes in cancer.
Lahtz C, Pfeifer GP. J Mol Cell Biol. 2011 Feb; 3(1):51-8.
Frequency of deletions of EPCAM (TACSTD1) in MSH2-associated Lynch syndrome cases. [J Mol Diagn. 2011]
Frequency of deletions of EPCAM (TACSTD1) in MSH2-associated Lynch syndrome cases.
Rumilla K, Schowalter KV, Lindor NM, Thomas BC, Mensink KA, Gallinger S, Holter S, Newcomb PA, Potter JD, Jenkins MA, et al. J Mol Diagn. 2011 Jan; 13(1):93-9. Epub 2010 Dec 23.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Gene (OMIM)
Gene records associated with Online Mendelian Inheritance in Man (OMIM) records that cite the current articles in their reference lists.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
OMIM (cited)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as reference cited at the end of the OMIM record.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

A hereditary nonpolyposis colorectal carcinoma case associated with hypermethyla...
A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor.
Cancer Res. 2002 Jul 15 ;62(14):3925-8.

PubMed
A survey of Cdk5 activator p35 and p25 levels in Alzheimer's disease brains.
A survey of Cdk5 activator p35 and p25 levels in Alzheimer's disease brains.
FEBS Lett. 2002 Jul 17 ;523(1-3):58-62.

PubMed
Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur...
Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur.
Neuroscience. 2002 ;113(1):155-66.

PubMed
Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth co...
Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology.
Neuron. 2002 Jul 3 ;35(1):51-63.

PubMed
A-to-I editing: new and old sites, functions and speculations.
A-to-I editing: new and old sites, functions and speculations.
Neuron. 2002 Jul 3 ;35(1):17-20.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to:

A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor.

Source

Abstract

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Supplemental Content

Save items

Related citations in PubMed

Cited by 25 PubMed Central articles

Related information

Recent activity

Simple NCBI Directory

Getting Started

Resources

Popular

Featured

NCBI Information