Abstract 2607: BPTF role in melanoma progression and BRAF resistance therapy

• Published in: Cancer research (Chicago, Ill.) Ill.), 2019-07, Vol.79 (13_Supplement), p.2607-2607
• Main Authors: Dar, Altaf A., Majid, Shahana, Semir, David de, Bezrookove, Vladimir, Nosrati, Mehdi, Kashani-Sabet, Mohammed
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2019-2607

Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we reveal new pro-oncogenic roles for BPTF in promoting tumor cell proliferation and resistance to targeted therapies. shRNA-mediated BPTF silencing suppressed the proliferative capacity (by 65.5%) and metastatic potential (by 66.4%) of melanoma cells. Elevated BPTF mean copy number greater than 3 was observed in 28 of 77 (36.4%) melanomas. BPTF overexpression predicted poor survival in a cohort of 311 melanoma patients (distant metastasis-free survival, p=0.03, and disease-specific survival p=0.008), and promoted resistance to BRAF inhibitors in melanoma cell lines. Metastatic melanoma tumors progressing on BRAF inhibitors contained low BPTF-expressing, apoptotic tumor cell sub-clones, indicating the continued presence of drug-responsive sub-clones within tumors demonstrating overall resistance to anti-BRAF agents. These studies demonstrate multiple pro-tumorigenic functions for BPTF, and identify it as a novel target for anti-cancer therapy. They also suggest the combination of BPTF targeting with BRAF inhibitors as a novel therapeutic strategy for melanomas with mutant BRAF. Citation Format: Altaf A. Dar, Shahana Majid, David de Semir, Vladimir Bezrookove, Mehdi Nosrati, Mohammed Kashani-Sabet. BPTF role in melanoma progression and BRAF resistance therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2607.