Molecular alterations and potential actionable mutations in peritoneal mesothelioma: a scoping review of high-throughput sequencing studies

M V Dietz*, J P van Kooten, M S Paats, J G V J Aerts, C Verhoef, E V E Madsen, H J Dubbink, J H von der Thüsen

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

3 Citations (Scopus)
18 Downloads (Pure)

Abstract

BACKGROUND:

Peritoneal mesothelioma (PeM) is a rare malignancy with a poor prognosis. Currently there is a lack of effective systemic therapies. Due to the rarity of PeM, it is challenging to study new treatment options. Off-label use of targeted drugs could be an effective approach. This scoping review aims to explore the genomic landscape of PeM to identify potential therapeutic targets.

MATERIALS AND METHODS:

A systematic literature search of Embase, Medline, Web of Science, the Cochrane Library, and Google Scholar was carried out up to 1 November 2022. Studies that reported on molecular alterations in PeM detected by high-throughput sequencing techniques were included. Genes that were altered in ≥1% of PeMs were selected for the identification of potential targeted therapies.

RESULTS: 

Thirteen articles were included, comprising 824 PeM patients. In total, 142 genes were altered in ≥1% of patients, of which 7 genes were altered in ≥10%. BAP1 was the most commonly altered gene (50%). Other commonly altered genes were NF2 (25%), CDKN2A (23%), CDKN2B (17%), PBRM1 (15%), TP53 (14%), and SETD2 (13%). In total, 17% of PeM patients were carriers of a germline mutation, mainly in BAP1 (7%).

CONCLUSIONS: 

This scoping review provides an overview of the mutational landscape of PeM. Germline mutations might be a larger contributor to the incidence of PeM than previously thought. Currently available targeted therapy options are limited, but several targeted agents [such as poly (ADP-ribose) polymerase (PARP), enhancer of zeste homolog 2 (EZH2), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors] were identified that might provide new targeted therapy options in the future.

Original languageEnglish
Article number101600
JournalESMO Open
Volume8
Issue number4
DOIs
Publication statusPublished - Aug 2023

Bibliographical note

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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