Inactivation of BAP1 and the Hippo Pathway Characterizes the Genomic Alterations of Peritoneal Mesothelioma

TL;DR

This study identifies BAP1 and Hippo pathway inactivation as key genomic features in peritoneal mesothelioma, a rare cancer with limited treatment options.

Contribution

The study reveals novel insights into the genomic alterations of peritoneal mesothelioma, highlighting potential therapeutic targets.

Findings

BAP1 gene mutations were the most common somatic mutation (25.98%).

NF2, TP53, and SETD2 genes also showed frequent mutations.

Chromatin remodeling, Hippo, and p53 signaling pathways are potential treatment targets.

Abstract

Background/Objectives: Peritoneal mesothelioma is a rare malignancy characterized by limited therapeutic options and a poor prognosis. Genomic characterization can enhance the understanding of the molecular mechanisms that lead to this disease and can contribute to improved survival outcomes through therapeutic targets. Methods: Analysis was performed using a dataset from the AACR GENIE database (v17.0-public) comprising 204 samples from 192 patients. Data were analyzed to identify patterns in genomic alterations and clinical demographics. Within the GENIE cohort, histologic subtype information was incomplete and inconsistently reported across contributing institutions. Hence, histological subtype genomic analysis was not viable. Results: The most common somatic mutation was found in the BAP1 gene (25.98%). Other common mutations were found in the NF2 (15.19%), TP53 (9.3%) and SETD2 (8.3%) genes. Several pathways were found as potential treatment targets including the chromatin remodeling, Hippo, and p53 signaling pathways. Given the size of our dataset, we were unable to draw significant conclusions about certain demographics. Conclusions: This study presents data that can help draw conclusions on common mutations, mutual exclusivity patterns, and demographics at risk for peritoneal mesothelioma. Genomic analysis of peritoneal mesothelioma may inform possible intervention targets for therapeutic treatment.

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