title: Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations.
abstract: BACKGROUND
  Genomic studies of malignant pleural mesothelioma (MPM) have recently identified frequent mutations in the BRCA-associated protein 1(BAP1) gene. In uveal melanoma and clear cell renal cell carcinoma, BAP1 mutations are associated with poor outcomes but their clinical significance in MPM is unknown. We therefore undertook this study to define the characteristics of patients whose MPM tumors harbor somatic BAP1 mutation and to examine the relationship between BAP1 mutation and survival.
  
  
  METHODS
  We reviewed the charts of 121 patients with MPM tumors diagnosed between 1991 and 2009 tested for BAP1 mutation, and extracted the following information: age at diagnosis, sex, histology, stage, smoking status, asbestos exposure, family or personal history of malignancy, and treatment including surgery, chemotherapy, and radiation as well as survival status.
  
  
  RESULTS
  Twenty-four of the 121 tumors (20%) harbored somatic BAP1 mutations. The percentage of current or former smokers among cases with BAP1 mutations was significantly higher than in BAP1 wild-type cases, (75% versus 42%; p = 0.006). However, the types of nucleotide substitutions in BAP1 did not suggest that this association was because of a causative role of smoking in BAP1 mutations. No other clinical feature was significantly different among those with and without BAP1 mutations in their MPM. There was also no difference in survival according to somatic BAP1 mutation status.
  
  
  CONCLUSIONS
  There is no apparent distinct clinical phenotype for MPM with somatic BAP1 mutation. The significance of the more frequent history of smoking among patients with BAP1-mutated MPM warrants further study.
authors.affiliation: *Department of Medicine, Division of Solid Tumor Oncology, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York; †Department of Medicine, Weill Cornell Medical College, New York, New York; ‡Departments of Pathology, §Surgery, ‖Epidemiology and Biostatistics, ¶Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Marjorie G
authors.initials: MG
authors.lastname: Zauderer
authors.forename: Matthew
authors.initials: M
authors.lastname: Bott
authors.forename: Robert
authors.initials: R
authors.lastname: McMillan
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Valerie
authors.initials: V
authors.lastname: Rusch
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase