Abstract 3056: Amplification of the BP1 homeobox gene in familial breast cancer with BRCA1/2 mutations

Abstract

Abstract Background: BP1 is a homeobox gene which was reported to be amplified and overexpressed in breast tumors with poor clinical outcome. Its exact role and function in breast tumorigenesis is not known and no studies have investigated its role in familial breast cancer cases. BP1 is located on 17q21, a chromosomal region that is altered in a high percentage of breast tumors; CGH analysis of the 17q region demonstrated gains in 50% and 85% of BRCA1 and BRCA2 mutated familial breast tumors, respectively. BP1 has been found to be overexpressed in breast cancer cells defective in double-strand break repair by homologous recombination (BRCA defective) and has been shown to directly regulate BRCA1 expression. The above information formed our rationale to evaluate the amplification of BP1 in familial breast cancer patients with known BRCA1/2 mutation status. We hypothesized that BP1 would be preferentially amplified in BRCA1/2 mutations carriers and correlated with poor clinical prognostic factors. Methods: Three tissue microarrays, containing tumor tissues of a total of 67 familial breast cancer patients, with known BRCA1/2, ER and PR status and full clinical data, were obtained from the Familial Cancer Registry from Georgetown University. FISH analysis was performed using a specific BP1 FISH probe developed in our lab. Results: FISH scoring in 100 cells was performed in 87% of the patients. Amplification of BP1 was observed in 26% of the cases and was significantly correlated with the presence of mutations in the BRCA1/2 genes, as opposed to patients with full negative (FN), Jewish panel negative (JPN) and variant with unknown significance (VUS). BP1 amplification was also significantly correlated with large tumor size (>1.5cm) and poorly differentiated tumors. Upon stratification of the samples by histological type, a total of 173 lesions (from cores containing different lesions from the same patients) were analyzed. Similar frequencies of BP1 amplification were observed in invasive (24%) and ductal carcinoma in situ (23.6%) lesions. Conclusions: Our findings demonstrate that the BP1 homeobox gene is amplified in familial breast cancer patients and its amplification is correlated with the presence of mutations in the BRCA1/2 genes as well as poor clinical prognostic factors, such as large tumor size and poorly differentiated tumors. Studies evaluating the expression of BRCA1 and BP1 proteins in these samples are in progress, in order to identify possible mechanism of interactions and related pathways between BP1 positive and BRCA1 mutant tumors in familial breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3056. doi:10.1158/1538-7445.AM2011-3056