Methylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter gene in triple-negative breast cancer patients

作者: Caterina Fumagalli , Giancarlo Pruneri , Paola Possanzini , Michela Manzotti , Monica Barile

DOI: 10.1007/S10549-011-1945-9

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摘要: Triple-negative breast cancers are characterized by the triple-negative (ER/PgR/Her2 negative) phenotype, frequently associated with BRCA gene mutation, and not candidate to currently available endocrine HER2-targeted treatments. MGMT is involved in direct DNA repair exerted cleavage of mutagenic alkyl adducts within DNA, its epigenetic silencing confers susceptibility DNA-damaging alkylating agents glioblastomas melanomas. methylation status has been extensively investigated cancer patients. The goal our study was evaluate TNBC patients, for most which BRCA1 BRCA2 mutational known. We evaluated methylation-specific PCR (MSP) formalin-fixed paraffin-embedded tumor specimens from 92 By using GelDoc system (Biorad) software, cases were further classified as follows: 0 (absence methylated signal), 1 (prevalence unmethylated signal, U/M ratio>1), 2 ratio<1), 3 signal). MSP products obtained 89 (96.7%) cases. Overall, 15 (16.9%) 0, 33 (37.1%) 1, 39 (43.8%) 2, (2.2%) 3. 48 considered unmethylated, 41 methylated. prevalence patients mutated, wild-type, unknown 30.2% (13/43), 63.6% (14/22), 58.3% (14/24), respectively. unrelated main clinical pathological characteristics, exception a weak association advanced age. In conclusion, data suggest that wild-type BRCA1, may be (63.6%) silenced methylation. evaluation could offer new adjunct predicting response drugs

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