The Genomic Landscape of Male Breast Cancers

Piscuoglio, S., Ng, C. K., Murray, M. P., Guerini-Rocco, E., Martelotto, L. G., Geyer, F. C., Bidard, F. C., Berman, S., Fusco, N., Sakr, R. A., Eberle, C., De Mattos-Arruda, L., Macedo, G. S., Akram, M., Baslan, T., Hicks, J., King, T. A., Brogi, E., Norton, L., Weigelt, B., Hudis, C. A., Reis-Filho, J. S. (March 2016) The Genomic Landscape of Male Breast Cancers. Clin Cancer Res, 22 (16). pp. 4045-56. ISSN 1078-0432 (Electronic)1078-0432 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/26960396
DOI: 10.1158/1078-0432.ccr-15-2840

Abstract

PURPOSE: Male breast cancer (MaBC) is rare and its genomic landscape has yet to be fully characterized. Lacking studies in men, treatment of MaBC patients is extrapolated from results in females with the disease (FBC). We sought to define whether MaBCs harbor somatic genetic alterations in genes frequently altered in FBCs. EXPERIMENTAL DESIGN: All MaBCs were estrogen receptor-positive and all but two were HER2 negative. 59 MaBCs were subtyped by immunohistochemistry and tumor-normal pairs were microdissected and subjected to massively parallel sequencing targeting all exons of 241 genes frequently mutated in FBCs or DNA-repair related. The repertoires of somatic mutations and copy number alterations of MaBCs were compared to that of subtype-matched FBCs. RESULTS: 29% and 71% of MaBCs were immunohistochemically classified as luminal A-like or luminal B-like, respectively. MaBCs displayed a heterogeneous repertoire of somatic genetic alterations that to some extent recapitulated that of estrogen receptor (ER)-positive/HER2-negative FBCs, including recurrent mutations affecting PIK3CA (20%) and GATA3 (15%). ER-positive/HER2-negative MaBCs, however, less frequently harbored 16q losses, and PIK3CA and TP53 mutations than ER-positive/HER2-negative FBCs. In addition, MaBCs were found to be significantly enriched for mutations affecting DNA repair-related genes. CONCLUSION: MaBCs less frequently harbor somatic genetic alterations typical of ER-positive/HER2-negative FBCs, such as PIK3CA and TP53 mutations and losses of 16q, suggesting that at least a subset of MaBCs are driven by a distinct repertoire of somatic changes. Given the genomic differences, caution may be needed in the application of biological and therapeutic findings from studies of FBCs to MaBCs.

Item Type: Paper
Subjects: bioinformatics
diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
organism description > animal > gender > male
CSHL Authors:
Communities: CSHL labs > Hicks lab
Depositing User: Matt Covey
Date: 9 March 2016
Date Deposited: 14 Mar 2016 19:39
Last Modified: 23 Sep 2016 20:21
PMCID: PMC4987160
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32437

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