Genomic Profiling of Tissue and Blood Predicts Survival Outcomes in Patients with Resected Pleural Mesothelioma

Details

• Personal Author:
  Arrieta O ; Cardona AF ; Culligan MJ ; de Miguel-Perez D ; Del Re M ; Friedberg JS ; Grier W ; Hirsch FR ; Malapelle U ; Mehra R ; Mohindra P ; Pepe F ; Pickering EM ; Pinto JA ; Pisapia P ; Rolfo C ; Russo A ; Russo G ; Sachdeva A ; Scilla KA ; Troncone G ; Wolf A
• Description:
  Purpose: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. Experimental Design: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. Results: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. Conclusions: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM. [Description provided by NIOSH]
• Subjects:
  Biomarkers Lung Neoplasms Occupational Health Respiratory System Safety
• Keywords:
  Author Keywords: Resected Pleural Mesothelioma Blood Mutations Gene Mutation Genetic Factors Genomics Mesothelioma Pleural Cavity Prognostic Biomarkers Tissue Mutations
• ISSN:
  0959-8049
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; New York ; Ohio ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  196
• NIOSHTIC Number:
  nn:20069686
• Citation:
  Eur J Cancer 2024 Jan; 196:113457
• Contact Point Address:
  Clinical Cancer Research, Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai Medical System & Icahn School of Medicine, Mount Sinai, 1470 Madison Ave, New York, NY 10029, USA
• Email:
  christian.rolfo@mssm.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Construction ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  European Journal of Cancer
• End Date:
  20260831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:797b13a5c809a9f1a24372af14a1fa5f384e0f87105989c2bd7567dcb34881e97b156faf4835059a644f65694345bd612eec789a10cffaefea2f21b0d8c2d374
• Download URL:
  https://stacks.cdc.gov/view/cdc/208063/cdc_208063_DS1.pdf
• File Type:
  [PDF - 3.34 MB ]