Deep sequencing analysis identified a specific subset of mutations distinctive of biphasic malignant pleural mesothelioma

Federica Torricelli, Filippo Lococo, Teresa Severina Di Stefano, Eugenia Lorenzini, Simonetta Piana, Riccardo Valli, Ottavio Rena, Giulia Veronesi, Andrea Billè, Alessia Ciarrocchi

Research output: Contribution to journalArticlepeer-review

Abstract

Malignant Pleural Mesothelioma (MPM) is a heterogeneous disease. Morphologically, three different phenotypes are distinguishable: epithelioid (e-), sarcomatoid (s-) and biphasic (biph-) MPM, the latest, being a mixture of e-and s-MPM cells. Being an intermediate entity, management of biph-MPM, remains debatable and controversial, with different guidelines recommending distinct approaches. Identification of biph-MPM associated genetic alterations, through deep sequencing analysis, may provide useful tools to understand these lesions. A retrospective cohort of 69 surgically resected MPMs, 39 biph-MPMs (56.5%) and 30 e-MPMs (43.5%) was selected. A separate set of 16 biph-MPM was used as validation set. Deep sequencing analysis on an MPM-specific custom panel (MPM_geneset) comprising 1041 amplicons spanning 34 genes was performed. A total of 588 variants and 5309 mutational events were detected. In total, 91.3% of MPMs showed at least one mutation and 76.8% showed co-occurrence of more than one alteration. Mutations in MXRA5 (p = 0.05) and NOD2 (p = 0.018) were significantly associated with biph-MPM both in the training and validation cohort and correlated with the extent of the sarcomatoid component. Mutations in NOD2 and XRCC6 correlated with patients’ survival. We demonstrated that biph-MPM are associated with a specific mutation set, and that genetic analysis at diagnosis may improve patients’ risk stratification.

Original languageEnglish
Article number2454
Pages (from-to)1-15
Number of pages15
JournalCancers
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Genetic mutations
  • Histotype
  • Malignant pleural mesothelioma
  • Next generation sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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