title: Absence of mutations in DNA mismatch repair genes in sporadic endometrial tumors with microsatellite instability.
abstract: DNA mismatch repair genes have been reported to play a role in the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC). Mutations of DNA mismatch repair genes have accounted for 90% of HNPCC-related colon and endometrial tumors. These mutations have been associated with microsatellite instability (MIN). Because endometrial cancer (EC) is the most common extracolonic malignancy associated with HNPCC, we hypothesized that similar molecular alterations may occur in sporadic endometrial tumors exhibiting MIN. Mutational analysis of the MSH2 and MLH1 genes was undertaken in sporadic EC that demonstrate MIN to determine the role of these genes in the pathogenesis of sporadic ECs. Established microsatellite markers were used to determine the incidence of MIN from 28 patients with sporadic EC. MIN was observed in 32% (9 of 28) of the tumor specimens analyzed. Mutational analysis of MSH2 and MLH1 genes was performed by immunohistochemical analysis and direct sequencing of tumor specimens that exhibited MIN. All 28 tumor specimens exhibited strong nuclear staining with both MSH2 and MLH1 antibodies, suggesting the absence of mutations. Sequencing of all exons of both the MSH2 and MLH1 genes in the nine MIN-positive tumor specimens demonstrated no mutations. We conclude that the MSH2 and MLH1 genes do not play a role in the pathogenesis of sporadic endometrial cancer.
authors.affiliation: Departments of Gynecologic Oncology Surgery, Laboratory Medicine & Pathology, Anatomical Pathology, and Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Lim
authors.forename: D
authors.initials: D
authors.lastname: Tester
authors.forename: W
authors.initials: W
authors.lastname: Cliby
authors.forename: S C
authors.initials: SC
authors.lastname: Ziesmer
authors.forename: P C
authors.initials: PC
authors.lastname: Roche
authors.forename: L
authors.initials: L
authors.lastname: Hartmann
authors.forename: S N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: K C
authors.initials: KC
authors.lastname: Podratz
authors.forename: R B
authors.initials: RB
authors.lastname: Jenkins
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1