title: Mismatch repair gene mutations in renal cell carcinoma.
abstract: We investigated the spectrum and genetic basis for mismatch repair (MMR) deficiency in renal cell carcinoma (RCC) by examining expression of four MMR genes important for hereditary and sporadic carcinogenesis. MMR deficiency was assessed using microsatellite instability (MSI) and genetic analyses of 25 cell lines derived from renal tumors. MMR gene alterations were detected using reverse transcription of RNA coupled with polymerase chain reaction (RT-PCR) and DNA sequencing. Three RCC lines with undetectable MLH1 were identified and investigated for MSI and inactivating mutations in the hMLH1 MMR gene. Genetic instability and hMLH1 mutations were identified in two RCC lines and their corresponding tumors. Genetic alterations affecting expression were limited to MLH1 since other MMR proteins (MSH2, MSH6 and PMS2) were detectable in our RCC lines. Complete inactivation of MMR is apparently uncommon in RCC and occurs predominantly through inactivating mutations in the hMLH1 gene.
authors.affiliation: Urologic Oncology Branch/NCI, National Institutes of Health, 10 Center Drive, Bldg.10/Room 2B47, Bethesda, MD 20892-1501, USA. leachf@mail.nih.gov
authors.forename: Fredrick S
authors.initials: FS
authors.lastname: Leach
authors.forename: Moon
authors.initials: M
authors.lastname: Koh
authors.forename: Kirti
authors.initials: K
authors.lastname: Sharma
authors.forename: Glenn
authors.initials: G
authors.lastname: McWilliams
authors.forename: LaTonia
authors.initials: L
authors.lastname: Talifero-Smith
authors.forename: Amanda
authors.initials: A
authors.lastname: Codd
authors.forename: Raul
authors.initials: R
authors.lastname: Olea
authors.forename: Ossama
authors.initials: O
authors.lastname: Elbahloul
mesh_terms: D020137:Base Pair Mismatch; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002893:Chromosomes, Human, Pair 3; D004260:DNA Repair / Q000235:genetics; D005091:Exons; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins