BCoR-L1variation and breast cancer

BRCA1 is involved in numerous essential processes in the cell, and the effects of BRCA1 dysfunction in breast cancer carcinogenesis are well described. Many of the breast cancer susceptibility genes such as BRCA2, p53, ATM, CHEK2, and BRIP1encode proteins that interact with BRCA1. BCL6 corepressor-like 1 (BCoR-L1) is a newly described BRCA1-interacting protein that displays high homology to several proteins known to be involved in the fundamental processes of DNA damage repair and transcription regulation. BCoR-L1 has been shown to play a role in transcription corepression, and expression of the X-linked BCoR-L1gene has been reported to be dysregulated in breast cancer subjects. BCoR-L1is located on the X chromosome and is subject to X inactivation. We performed mutation analysis of 38 BRCA1/2mutation-negative breast cancer families with male breast cancer, prostate cancer, and/or haplotype sharing around BCoR-L1to determine whether there is a role for BCoR-L1as a high-risk breast cancer predisposition gene. In addition, we conducted quantitative real-time PCR (qRT-PCR) on lymphoblastoid cell lines (LCLs) from the index cases from these families and a number of cancer cell lines to assess the role of BCoR-L1dysregulation in cancer and cancer families. Very little variation was detected in the coding region, and qRT-PCR analysis revealed that BCoR-L1expression is highly variable in cancer-free subjects, high-risk breast cancer patients, and cancer cell lines. We also report the investigation of a new expression control, DIDO1(death inducer-obliterator 1), that is superior to GAPDH(glyceraldehyde-3-phosphate dehydrogenase) and UBC(ubiquitin C) for analysis of expression in LCLs. Our results suggest that BCoR-L1expression does not play a large role in predisposition to familial breast cancer.