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. 2023 Aug;8(4):101600.
doi: 10.1016/j.esmoop.2023.101600. Epub 2023 Jul 13.

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

M V Dietz  1 , J P van Kooten  2 , M S Paats  3 , J G V J Aerts  3 , C Verhoef  2 , E V E Madsen  2 , H J Dubbink  4 , J H von der Thüsen  4
Affiliations

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

M V Dietz et al. ESMO Open. 2023 Aug.

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.

Keywords: germline mutations; molecular alterations; peritoneal mesothelioma; targeted therapies.

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Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) flow diagram. PeM, peritoneal mesothelioma.
Figure 2
Figure 2
Gene alterations present in ≥1% of the peritoneal mesothelioma (PeM) patients.
See this image and copyright information in PMC

References

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