MLH3 mutation in endometrial cancer. Cancer Res 2006 Aug 01;66(15):7502-8
Date
08/04/2006Pubmed ID
16885347DOI
10.1158/0008-5472.CAN-06-0248Scopus ID
2-s2.0-33747892726 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
MLH3 is a recently described member of the DNA mismatch repair gene family. Based on its interaction with the MutL homologue MLH1, it was postulated that MLH3 might play a role in tumorigenesis. Germ line and somatic mutations in MLH3 have been identified in a small fraction of colorectal cancers, but the role of MLH3 in colorectal cancer tumorigenesis remains controversial. We investigated MLH3's role in endometrial tumorigenesis through analysis of tumor and germ line DNA from 57 endometrial cancer patients who were at increased risk for having inherited cancer susceptibility. Patients with known MSH2 or MSH6 mutations were excluded as well as those who had MLH1-methylated tumors. Sixteen different variants were identified by single-strand conformational variant analysis. Of the 12 missense changes identified, three were somatic mutations. One patient had a germ line missense variant and loss of heterozygosity (LOH) in her tumor specimen. There was no evidence of MLH3 promoter methylation based on combined bisulfite restriction analysis. The identification of inherited missense variants, somatic missense mutations (present in 3 of 57 tumors), and LOH in the tumor from a patient with a germ line missense change suggest a role for MLH3 in endometrial tumorigenesis.
Author List
Taylor NP, Powell MA, Gibb RK, Rader JS, Huettner PC, Thibodeau SN, Mutch DG, Goodfellow PJAuthor
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Base SequenceCarrier Proteins
Case-Control Studies
Cohort Studies
DNA Methylation
Endometrial Neoplasms
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Loss of Heterozygosity
Middle Aged
MutL Proteins
Mutation
Mutation, Missense
Promoter Regions, Genetic