Project description:Diagnostic samples from female breast cancer patients with ER-positive and HER2-normal tumors selected for neoadjuvant chemotehrapy.
Project description:In this experiment, formalin-fixed paraffin-embedded male (n=15) and female (n=10) primary invasive ductal carcinoma (all ERα-positive, HER2-negative, node-negative) samples were selected and hybridized using the Almac Diagnostics Breast Cancer DSA(TM) array ADXBRCv2a520413 in order to investigate the gene expression differences between male and female breast cancer.
Project description:About 25% of familial breast cancer (BC) is attributed to germline mutations of BRCA1 and BRCA2 genes while the rest of patients are included in the BRCAX group. BC also affects men with a worldwide incidence of 1%. The epigenetic alterations, including those DNA methylation, have been rarely studied in the male breast cancer (MBC) on a genome-wide level. The aim of the current work was to study the global DNA methylation profiles of BC patients to look for differences between familial female breast cancer (FBC) and MBC and according to BRCA1, BRCA2 and BRCAX mutation status. The genomic DNA from FFPE tissues of 17 female and 7 male patients with BC was subjected to methylated DNA immunoprecipitation (MeDIP) and hybridized on human promoter microarrays. The comparison between FBC and MBC showed 2846 differentially methylated regions (DMRs) corresponding to 2486 distinct annotated genes. The gene ontology enrichment analysis revealdrelevant molecular function terms such as the GTPase superfamily genes (in particular the GTPase Rho GAP/GEF and GTPase RAB) and cellular component terms associated to cytoskeletal architecture such as “cytoskeletal part”, “keratin filament”, “intermediate filament". By considering only FBC, several cancer-associated pathways were the most enriched KEGG pathways of differentially methylated genes between BRCA2 and BRCAX or BRCA1+BRCAX groups. The comparison between BRCA1 group vs BRCA2+BRCAX group displayed the enriched molecular function term “cytoskeletal protein binding”. Finally, the functional annotation of differentially methylated genes between BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were related to GTPase activity. In summary, this is the first study that compares the global DNA methylation profile of familial FBC and MBC and the results may provide useful insights into the epigenomic subtyping of breast cancer and shed light on a possible new molecular mechanisms underlying BC carcinogenesis.
Project description:Female breast cancer patients who underwent surgery for breast cancer as part of the Danish Center for Translational Breast Cancer Research program were included from 2003 to 2012. Patient inclusion criteria were: (1) a unifocal tumor with an estimated size of more than 20 mm in diameter, (2) none of the patients had a history of breast surgery and (3) none received preoperative treatment. Patients were defined as high risk according to the Danish Breast Cooperative Group (www.dbcg.dk) and were followed after surgery.