Isolated BAP1 Genomic Alteration in Malignant Pleural Mesothelioma Predicts Distinct Immunogenicity with Implications for Immunotherapeutic Response

Details

• Personal Author:
  Becich MJ ; Osmanbeyoglu HU ; Palmer D ; Sagan A ; Sementino E ; Testa JR
• Description:
  Malignant pleural mesothelioma (MPM), an aggressive cancer of the mesothelial cells lining the pleural cavity, lacks effective treatments. Multiple somatic mutations and copy number losses in tumor suppressor genes (TSGs) BAP1, CDKN2A/B, and NF2 are frequently associated with MPM. The impact of single versus multiple genomic alterations of TSG on MPM biology, the immune tumor microenvironment, clinical outcomes, and treatment responses are unknown. Tumors with genomic alterations in BAP1 alone were associated with a longer overall patient survival rate compared to tumors with CDKN2A/B and/or NF2 alterations with or without BAP1 and formed a distinct immunogenic subtype with altered transcription factor and pathway activity patterns. CDKN2A/B genomic alterations consistently contributed to an adverse clinical outcome. Since the genomic alterations of only BAP1 was associated with the PD-1 therapy response signature and higher LAG3 and VISTA gene expression, it might be a candidate marker for immune checkpoint blockade therapy. Our results on the impact of TSG genotypes on MPM and the correlations between TSG alterations and molecular pathways provide a foundation for developing individualized MPM therapies. [Description provided by NIOSH]
• Subjects:
  Genetics Immune System Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Tumor Suppressor Gene Loss BAP1 Cancer Genes Genetic Factors Genotype Immune System Immunology Malignant Pleural Mesothelioma Mesothelioma Survival Rate

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• ISSN:
  2072-6694
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  14
• Issue:
  22
• NIOSHTIC Number:
  nn:20067099
• Citation:
  Cancers 2022 Nov; 14(22):5626
• Contact Point Address:
  Hatice Ulku Osmanbeyoglu, Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15206, USA
• Email:
  osmanbeyogluhu@pitt.edu
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Construction ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Cancers
• End Date:
  20260831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:60a2da5ca9902603e79c57166b55e5c73db08d022dfec2638cfe0f700aa3b4f77e33f9d65525d4848c1a2fc98e22f7f93fc8b589bce3e8dd2cf7bae1e79acf85
• Download URL:
  https://stacks.cdc.gov/view/cdc/231291/cdc_231291_DS1.pdf
• File Type:
  [PDF - 2.26 MB ]