Genome-based Mutational Analysis by Next Generation Sequencing in Patients with Malignant Pleural and Peritoneal Mesothelioma

Anticancer Res. 2016 May;36(5):2331-8.

Abstract

Background/aim: Malignant mesothelioma is a rare malignancy with limited therapeutic options. Exome-based next-generation sequencing (NGS) techniques may direct the future of molecular targeting and improve systemic therapies for patients with mesothelioma.

Materials and methods: Eleven patients with NGS testing were selected, with a total of 236 somatic cancer-related mutations analyzed. Descriptive and Kaplan-Meier statistics were applied.

Results: The median age was 65 years (range=27-73 years); 4 (36%) patients were females. Seven (64%) and four patients (36%) had pleural and peritoneal mesothelioma, respectively. Detectable mutations were found in 86% of the pleural and 50% of the peritoneal mesothelioma patients (overall, 73% of patients). The families of BAP1 (36%), CDKNA2A/B (27%) and NF2 (27%) represented the most frequently mutated genes. The median overall survival for all patients was 20.8 months, with 1- and 2-year survival rates of 91% and 40%, respectively.

Conclusion: Genomic alterations as potential therapeutic targets were found by NGS. These findings will help in the development of new screening tools and targeting therapies, and in turn impact the standard-of-care and potentially lengthen disease control and survival periods in the future.

Keywords: BAP1; CDKNA2A/B; Malignant mesothelioma; NF2; molecular targeting therapy; next-generation sequencing.

MeSH terms

  • Adult
  • Aged
  • Asbestosis / complications
  • DNA Mutational Analysis / methods*
  • DNA, Neoplasm / genetics*
  • Female
  • Genes, Neoplasm
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lymphoma / genetics
  • Male
  • Mesothelioma / genetics*
  • Mesothelioma / mortality
  • Mesothelioma, Malignant
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Second Primary / genetics
  • Peritoneal Neoplasms / genetics*
  • Peritoneal Neoplasms / mortality
  • Pleural Neoplasms / genetics*
  • Pleural Neoplasms / mortality
  • Sequence Analysis, DNA*

Substances

  • DNA, Neoplasm
  • Neoplasm Proteins