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Title: Mutational profiling of familial male breast cancers reveals similarities with luminal A female breast cancer with rare TP53 mutations.
Austin Authors: Deb, Siddhartha;Wong, S Q;Li, J ;Do, Hongdo;Weiss, J ;Byrne, D;Chakrabarti, A;Bosma, T;Fellowes, A;Dobrovic, Alexander ;Fox, S B
Institutional Author: kConFab Investigators
Affiliation: Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Department of Pathology, University of Melbourne, Parkville, VIC 3010, Australia
Molecular Diagnostics, Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia
Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia
Department of Molecular Pathology, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia
Department of Bioinformatics, Cancer Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC 3010, Australia
Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Issue Date: 9-Dec-2014
Publication information: British Journal of Cancer; 111(12): 2351-60
Abstract: Male breast cancer (MBC) is still poorly understood with a large proportion arising in families with a history of breast cancer. Genomic studies have focused on germline determinants of MBC risk, with minimal knowledge of somatic changes in these cancers.Using a TruSeq amplicon cancer panel, this study evaluated 48 familial MBCs (3 BRCA1 germline mutant, 17 BRCA2 germline mutant and 28 BRCAX) for hotspot somatic mutations and copy number changes in 48 common cancer genes.Twelve missense mutations included nine PIK3CA mutations (seven in BRCAX patients), two TP53 mutations (both in BRCA2 patients) and one PTEN mutation. Common gains were seen in GNAS (34.1%) and losses were seen in GNAQ (36.4%), ABL1 (47.7%) and ATM (34.1%). Gains of HRAS (37.5% vs 3%, P=0.006), STK11 (25.0% vs 0%, P=0.01) and SMARCB1 (18.8% vs 0%, P=0.04) and the loss of RB1 (43.8% vs 13%, P=0.03) were specific to BRCA2 tumours.This study is the first to perform high-throughput somatic sequencing on familial MBCs. Overall, PIK3CA mutations are most commonly seen, with fewer TP53 and PTEN mutations, similar to the profile seen in luminal A female breast cancers. Differences in mutation profiles and patterns of gene gains/losses are seen between BRCA2 (associated with TP53/PTEN mutations, loss of RB1 and gain of HRAS, STK11 and SMARCB1) and BRCAX (associated with PIK3CA mutations) tumours, suggesting that BRCA2 and BRCAX MBCs may be distinct and arise from different tumour pathways. This has implications on potential therapies, depending on the BRCA status of MBC patients.
Gov't Doc #: 25490678
DOI: 10.1038/bjc.2014.511
Journal: British Journal of Cancer
Type: Journal Article
Subjects: BRCA1 Protein.genetics
BRCA2 Protein.genetics
Breast Neoplasms, Male.enzymology.genetics.metabolism
DNA Mutational Analysis
Genes, p53
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
PTEN Phosphohydrolase.genetics
Tumor Suppressor Protein p53.genetics
Appears in Collections:Journal articles

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