TY - JOUR
T1 - Clinical characteristics of patients with malignant pleural mesothelioma harboring somatic BAP1 mutations
AU - Zauderer, Marjorie G.
AU - Bott, Matthew
AU - Mcmillan, Robert
AU - Sima, Camelia S.
AU - Rusch, Valerie
AU - Krug, Lee M.
AU - Ladanyi, Marc
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/11
Y1 - 2013/11
N2 - INTRODUCTION:: 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. CONCLUSION:: 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.
AB - INTRODUCTION:: 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. CONCLUSION:: 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.
KW - BRCA-associated protein 1
KW - Mesothelioma
KW - Novel therapeutics
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U2 - 10.1097/JTO.0b013e31829e7ef9
DO - 10.1097/JTO.0b013e31829e7ef9
M3 - Article
C2 - 24128712
AN - SCOPUS:84886466708
SN - 1556-0864
VL - 8
SP - 1430
EP - 1433
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 11
ER -