Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas.

Publication Type:

Journal Article

Source:

Molecular cancer, Volume 8, p.48 (2009)

Keywords:

2009, Adaptor Proteins, Signal Transducing, Antineoplastic Combined Chemotherapy Protocols, Apoptosis Regulatory Proteins, BRCA1 Protein, BRCA2 Protein, Bridged Compounds, Center-Authored Paper, DNA Methylation, DNA repair, Fanconi Anemia Complementation Group F Protein, Female, Human Biology Division, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Mutation, Neoplasm Recurrence, Local, Nuclear Proteins, Organoplatinum Compounds, Ovarian Neoplasms, Promoter Regions, Genetic, Proportional Hazards Models, Public Health Sciences Division, Taxoids, Tumor Suppressor Protein p53

Abstract:

DNA repair genes critically regulate the cellular response to chemotherapy and epigenetic regulation of these genes may be influenced by chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115 sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms collected after chemotherapy. Additionally, we assessed whether promoter methylation of BRCA1, MLH1 or FANCF influenced response to chemotherapy or explained alterations in protein expression after chemotherapy exposure.