Clustering of Lynch syndrome malignancies with no evidence for a role of DNA mismatch repair.

ABSTRACT:

Objectives

We ascertained a large kindred with an excess of Lynch syndrome-associated cancers. Our objective was to determine if a defect in one of the DNA mismatch repair (DMMR) genes was the probable cause of cancer susceptibility as microsatellite instability (MSI) and immunohistochemical (IHC) analysis of the probands' tumors did not provide a clear indication.

Methods

A detailed history and review of medical records was undertaken to construct a four-generation pedigree. Blood samples were obtained for analysis of germline DNA. Polymorphic repeats from the MLH1, MSH2, MSH6, and PMS2 loci were genotyped and the co-segregation of markers and disease was assessed. DMMR gene expression for all available tumors was evaluated by IHC. Combined bisulfite restriction analysis (C

SUBMITTER: Case AS 

PROVIDER: S-EPMC3023170 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature