Abstract 446: BAP1 mutation in mesothelioma and “BAP1 Cancer Syndrome”

Abstract

Abstract Malignant mesothelioma (MM) is a lethal cancer whose pathogenesis results from complex interactions between host genetics and environmental carcinogens, such as asbestos and erionite fibers. Recently, BAP1 (BRCA associated protein 1) has been identified as a novel MM tumor suppressor gene located at 3p21, a region frequently deleted in MM, which encodes for a deubiquitinase enzyme known to target histones and other proteins. We discovered that germline BAP1 mutations cause a novel cancer syndrome characterized by a significant excess of both pleural and peritoneal MM, uveal and cutaneous melanoma and possibly other tumors. In the same study, we reported that 22% sporadic MM tumors, among the Caucasian population, harbored somatic BAP1 mutations. Several other studies supported a relevant role of BAP1 in MM. However, a significant variation in the frequency of BAP1 mutation was found across different studies and populations. In fact, one research group found BAP1 gene altered in 61% of tumor samples from a Japanese cohort, pointing out to a possible influence of ethnicity on the prevalence of BAP-1 alterations among MM patients. However, the limitations in tumor sample sizes and methodological differences across studies do not allow for conclusive associations. We are now further analyzing BAP1 status and possible clinicopathological associations using different and more sensitive methods, such as MPLA, DNA and RNA sequencing, DNA copy number and methylation. Our preliminary results indicate that, regardless of ethnicity, BAP1 plays a crucial role in MM pathogenesis. More experiments are urgently needed to see whether BAP1 expression could be used in diagnostic, prognostic, or therapeutic settings. The impact of this work will extend to other cancers with BAP1 mutations. Citation Format: Masaki Nasu, Andrea Napolitano, Sandra Pastorino, Mika Tanji, Erin Flores, Francine Baumann, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Haining Yang, Michele Carbone. BAP1 mutation in mesothelioma and “BAP1 Cancer Syndrome”. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 446. doi:10.1158/1538-7445.AM2014-446