title: Gene expression profile and mutational analysis of DNA mismatch repair genes in carcinoma prostate in Indian population.
abstract: DNA mismatch repair (MMR) plays a role in promoting genetic stability by repairing DNA replication errors, inhibiting recombination between nonidentical DNA sequences, and participating in responses to DNA damage. Although the role of MMR in prostate carcinogenesis remains unclear, MMR deficiency in Carcinoma Prostate (Pca) could prove to be clinically significant. Thus, the present study investigated the gene expression profile of six major MMR genes, viz. hMLH1, hMSH2, hPMS1, hPMS2, hMSH3, and hMSH6, and polymorphism in hMLH1 and hMSH2 in Pca in Indian population. Further, correlation with clinicopathological parameters was evaluated to establish their role as a potential prognostic marker. A significant downregulation of hMLH1, hMSH2, and hPMS2 expression was observed in Pca compared to benign prostatic hyperplasia (BPH). A greater loss of hPMS2 protein in poorly differentiated tumors was demonstrated, which was in concordance with a significant inverse correlation of hPMS2 gene expression with the Gleason score indicating its significance as a marker for Pca progression. An important association of hMLH1-93G>A polymorphism with the risk of Pca was also identified. The results of the present study suggest that an altered MMR has important biological and clinical significance in Pca in Indian population.
authors.affiliation: Institute of Pathology, Indian Council of Medical Research, Tumour Biology, New Delhi, India.
authors.forename: Abha
authors.initials: A
authors.lastname: Soni
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: L C
authors.initials: LC
authors.lastname: Singh
authors.forename: Ashwani K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Mainak
authors.initials: M
authors.lastname: Majumdar
authors.forename: Thoudam
authors.initials: T
authors.lastname: Regina
authors.forename: N K
authors.initials: NK
authors.lastname: Mohanty
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000483:Alleles; D002277:Carcinoma / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein