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Emerging roles of BRCA1 alternative splicing

National Institute of Oncology, Department of Molecular Genetics, Budapest, H-1122, Hungary

Correspondence to:
T I Orban, National Institute of Oncology, Department of Molecular Genetics, Rath Gy. u. 7–9, Budapest, H-1122, Hungary;
orbi{at}oncol.hu

ABSTRACT
Germline mutations of the BRCA1 gene predispose individuals mainly to the development of breast and/or ovarian cancer. However, the exact function of the gene is still unclear, although the encoded proteins are involved in various cellular processes, including transcriptional regulation and DNA repair pathways. Several BRCA1 splice variants are found in different tissues, but in spite of intense investigations, their regulation and possible functions are poorly understood at the moment. This review summarises current knowledge on the roles of these splice variants and the mechanisms responsible for their formation. Because alternative splicing is now widely accepted as an important source of genetic diversity, elucidating the functions of the BRCA1 splice variants would help in the understanding of the exact role(s) of this tumour suppressor. This should help to resolve the current paradox that, despite its seemingly vital cellular functions, mutations of this gene are associated with tissue specific tumour formation predominantly in the breast and the ovary.

Keywords: BRCA1; alternative splicing; breast cancer; ovarian cancer

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