Clinical characteristics of patients with malignant pleural mesothelioma (MPM) harboring somatic BAP1 mutations.

Abstract

1541 Background: Efforts to elucidate tumorigenic mutations in MPM are essential to advance therapy. We reported a 23% incidence of somatic mutations in BRCA1-associated protein-1 (BAP1) in 53 patients with MPM (Bott et al. Nat Genet 2011). Germline BAP1 mutations were also reported in two families with a predisposition to mesothelioma and uveal melanoma (Testa et al. Nat Genet 2011). While BAP1 somatic mutations are more common in poor prognosis uveal melanoma (84% class 2, 4% class 1; Harbour et al. Science 2010), the significance of these mutations in MPM is unknown. Therefore, we analyzed the clinical characteristics of patients with somatic BAP1 mutations in order to describe this newly identified subpopulation. Methods: We reviewed the charts of 121 patients with tumors tested for somatic BAP1 mutations. Results: Patient characteristics are in the Table. Twenty percent harbored somatic BAP1 mutations. Other than the percent of current or former smokers (75% BAP1 mutations, 42% BAP1 wild-type, p=0.006), no other clinical feature was significantly different among those with and without BAP1 mutations. Among 53 samples analyzed for NF2 mutation and p16 deletion, no correlation was seen with BAP1 mutation. Conclusions: Somatic BAP1 mutations occur in about 20% of MPM tumors. Aside from smoking history, no other differences in clinical characteristics or outcomes were noted in the BAP1 mutated cases. Similar efforts are needed to describe the features of germline mutations in order to define this new cancer predisposition syndrome. We are planning a prospective trial to further evaluate the prevalence of germline BAP1 mutations, and we are also exploring the therapeutic implications. [Table: see text]