1. BRCA2 carriers with male breast cancer show elevated tumour methylation
- Author
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Elena A Takano, Siddhartha Deb, Alexander Dobrovic, David J Byrne, kConFab Investigators, Stephen B. Fox, Kylie L. Gorringe, and Jia-Min B Pang
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,Heterozygote ,Cancer Research ,medicine.medical_specialty ,lcsh:RC254-282 ,Methylation ,Breast Neoplasms, Male ,03 medical and health sciences ,GSTP1 ,Twist transcription factor ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Genetics ,medicine ,Humans ,Promoter Regions, Genetic ,Aged ,Aged, 80 and over ,BRCA2 Protein ,BRCA1 Protein ,business.industry ,Twist-Related Protein 1 ,Nuclear Proteins ,Cancer ,DNA Methylation ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,BRCA1 ,Promoter methylation ,medicine.disease ,BRCA2 ,Neoplasm Proteins ,Male breast cancer ,030104 developmental biology ,Invasive carcinoma of no special type ,030220 oncology & carcinogenesis ,Mutation ,DNA methylation ,Cancer research ,Familial breast cancer ,business ,Research Article - Abstract
Background Male breast cancer (MBC) represents a poorly characterised group of tumours, the management of which is largely based on practices established for female breast cancer. However, recent studies demonstrate biological and molecular differences likely to impact on tumour behaviour and therefore patient outcome. The aim of this study was to investigate methylation of a panel of commonly methylated breast cancer genes in familial MBCs. Methods 60 tumours from 3 BRCA1 and 25 BRCA2 male mutation carriers and 32 males from BRCAX families were assessed for promoter methylation by methylation-sensitive high resolution melting in a panel of 10 genes (RASSF1A, TWIST1, APC, WIF1, MAL, RARβ, CDH1, RUNX3, FOXC1 and GSTP1). An average methylation index (AMI) was calculated for each case comprising the average of the methylation of the 10 genes tested as an indicator of overall tumour promoter region methylation. Promoter hypermethylation and AMI were correlated with BRCA carrier mutation status and clinicopathological parameters including tumour stage, grade, histological subtype and disease specific survival. Results Tumours arising in BRCA2 mutation carriers showed significantly higher methylation of candidate genes, than those arising in non-BRCA2 familial MBCs (average AMI 23.6 vs 16.6, p = 0.01, 45% of genes hypermethylated vs 34%, p
- Published
- 2017
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