title: Clinical significance of epigenetic inactivation of hMLH1 and BRCA1 in Tunisian patients with invasive breast carcinoma.
abstract: Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) and BRCA1 (breast cancer 1, early onset) in 78 primary breast cancers from Tunisian patients. The methylation frequencies were 24.36% for hMLH1 and 46% for BRCA1. BRCA1 methylation correlated with age at diagnosis (P = .015) and 5-years disease free survival (P = .016) while hMLH1 methylation was more frequent in larger tumors (P = .002) and in presence of distant metastasis (P = .004). Furthermore, methylation of hMLH1 significantly correlated with high level of P53 expression (P = .006) and with overall survival (P = .015) suggesting that silencing of hMLH1 through aberrant promoter methylation could be used as a poor prognosis indicator in breast cancer.
authors: Unitéde Génétique du cancer et Production de protéines thérapeutiques, Centre de Biotechnologie de Sfax, route Sidi Mansour, BP 1177, 3018 Sfax, Tunisia.
authors: Sondes
authors: S
authors: Karray-Chouayekh
authors: Fatma
authors: F
authors: Trifa
authors: Abdelmajid
authors: A
authors: Khabir
authors: Nouredine
authors: N
authors: Boujelbane
authors: Tahia
authors: T
authors: Sellami-Boudawara
authors: Jamel
authors: J
authors: Daoud
authors: Mounir
authors: M
authors: Frikha
authors: Ali
authors: A
authors: Gargouri
authors: Raja
authors: R
authors: Mokdad-Gargouri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014416:Tunisia
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D000070957:MutL Protein Homolog 1