High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma

Details

• Alternative Title:
  J Thorac Oncol
• Personal Author:
  Nasu, Masaki ; Emi, Mitsuru ; Pastorino, Sandra ; Tanji, Mika ; Powers, Amy ; Luk, Hugh ; Baumann, Francine ; Zhang, Yu-an ; Gazdar, Adi ; Kanodia, Shreya ; Tiirikainen, Maarit ; Flores, Erin ; Gaudino, Giovanni ; Becich, Michael J. ; Pass, Harvey I. ; Yang, Haining ; Carbone, Michele
• Description:
  Background
  
  BAP1 is a nuclear deubiquitinase that regulates gene expression, transcription, DNA repair, and more. Several findings underscore the apparent “driver” role of BAP1 in malignant mesothelioma (MM). However the reported frequency of somatic BAP1 mutations in MM varies considerably, a discrepancy that appeared related to either methodological or ethnical differences across various studies.
  
  Methods
  
  To address this discrepancy, we carried out comprehensive genomic and immunohistochemical (IHC) analyses to detect somatic BAP1 gene alterations in 22 frozen MM biopsies from US MM patients.
  
  Results
  
  By combining Sanger sequencing, Multiplex Ligation-Dependent Probe Amplification, copy number analysis and cDNA sequencing, we found alteration of BAP1 in 14/22 biopsies (63.6%). No changes in methylation were observed. IHC revealed normal nuclear BAP1 staining in the 8 MM containing wild-type BAP1, while no nuclear staining was detected in the 14 MM biopsies containing tumor cells with mutated BAP1. Thus, IHC results were in agreement with those obtained by genomic analyses. We then extended IHC analysis to an independent cohort of 70 MM biopsies, of which there was insufficient material to perform molecular studies. IHC revealed loss of BAP1 nuclear staining in 47 out of these 70 MM biopsies (67.1%).
  
  Conclusions
  
  Our findings conclusively establish BAP1 as the most commonly mutated gene in MM, regardless of ethnic background or other clinical characteristics. Our data point to IHC as the most accessible and reliable technique to detect BAP1 status in MM biopsies.
  
  
• Subjects:
  Adult Aged Article Biopsy DNA, Neoplasm Female Humans Immunohistochemistry Incidence Lung Neoplasms Male Mesothelioma Middle Aged MLPA Mutation New York Pleural Neoplasms Prognosis Real-Time Polymerase Chain Reaction Somatic BAP1 Mutation Sporadic Malignant Mesothelioma Tumor Cells, Cultured Tumor Suppressor Proteins Ubiquitin Thiolesterase Young Adult

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• Source:
  J Thorac Oncol. 10(4):565-576.
• Pubmed ID:
  25658628
• Pubmed Central ID:
  PMC4408084
• Document Type:
  Journal Article
• Funding:
  2U24-OH009077-08/OH/NIOSH CDC HHS/United States ; P01 CA114047/CA/NCI NIH HHS/United States ; P01CA114047/CA/NCI NIH HHS/United States ; P30 CA071789/CA/NCI NIH HHS/United States ; P30CA071789/CA/NCI NIH HHS/United States ; R01 CA160715/CA/NCI NIH HHS/United States ; R01CA106567/CA/NCI NIH HHS/United States ; R01CA160715-0A/CA/NCI NIH HHS/United States
• Volume:
  10
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b07a9b711ba069b96a6acd3ef16a6d37ab7a0509c8de0901bdf961373bb3023d
• Download URL:
  https://stacks.cdc.gov/view/cdc/30878/cdc_30878_DS1.pdf
• File Type:
  [PDF - 1.50 MB ]