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Molecular And Genomic Characterization Of A Newly Established Male Breast Cancer Cell Line

CANCER RESEARCH(2017)

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Abstract
Although the majority of breast cancers affect women, approximately 1% of cases occur in men. At present comparatively little is known about the molecular mechanisms that influence male breast cancer predisposition and tumorigenicity. This is largely due to the current unavailability of an established cell line model in which to study male breast cancer. Development of in vitro models of the disease is therefore warranted, not least because growing evidence indicates that it is sufficiently different from female breast cancer such that extrapolating knowledge from one to the other may be misleading. Here we report the establishment and characterisation of a male breast cancer cell line derived from a primary tumor arising in a 61-year old male patient. We used 3T3-J2 mouse fibroblast co-culture in the presence of a ROCK inhibitor to conditionally reprogram epithelial cells from freshly resected tumor tissue. Once established, the cell line showed a rapid proliferation rate and growth in full conditioned media without the support of mouse fibroblasts. Immunohistochemical profiling demonstrated expression of epithelium-specific antigens AE1/AE3, breast epithelial marker CK7 and confirmed estrogen receptor positivity in concordance with the primary tumor. Germline sequencing detected no pathogenic germline predisposition mutations in either BRCA1 or BRCA2. There was no evidence of somatic mutation in any of the established female breast cancer driver genes. Somatic whole genome sequencing of early and late passages indicated a paucity of structural aberration and little evidence for obvious accumulation of gross genetic alterations. In conclusion, we have established a novel in vitro model for studying male breast cancer. That the cell line genome displays minimal evidence of significant acquired genetic changes arising due to reprogramming suggests that it will be of value in future studies of the biology of male breast cancer. Citation Format: Tereza Vaclova, Sarah Maguire, Matthew Pugh, Peter Barry, Nick Orr. Molecular and genomic characterization of a newly established male breast cancer cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 816. doi:10.1158/1538-7445.AM2017-816
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Key words
breast cancer,genomic characterization,line
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