Genomic landscape of pleural mesothelioma in Japanese patients: A comprehensive analysis using nationwide database

TL;DR

This study analyzes the genomic profiles of Japanese pleural mesothelioma patients to identify genetic alterations and potential biomarkers for prognosis and treatment.

Contribution

The first large-scale genomic characterization of Japanese pleural mesothelioma patients using a nationwide database.

Findings

Frequent genetic alterations in BAP1, NF2, TP53, CDKN2A/B, and MTAP were identified.

High TMB and TP53 alterations were linked to poor prognosis.

Immune checkpoint inhibitors improved overall survival in patients.

Abstract

•Large-scale genomic profiling of Japanese patients with pleural mesothelioma.•Frequent alterations identified in BAP1, NF2, TP53, CDKN2A/B, and MTAP.•High TMB and TP53 alterations were associated with poor prognosis.•Immune checkpoint inhibitor treatment improved overall survival.

Large-scale genomic profiling of Japanese patients with pleural mesothelioma.

Frequent alterations identified in BAP1, NF2, TP53, CDKN2A/B, and MTAP.

High TMB and TP53 alterations were associated with poor prognosis.

Immune checkpoint inhibitor treatment improved overall survival.

Pleural mesothelioma (PM) is a rare and aggressive malignancy. The development of novel therapeutic strategies targeting PM remains an unmet clinical need. However, comprehensive genomic data from Asian populations, particularly from Japanese patients, are limited. This study aimed to elucidate the genomic landscape of PM in Japanese patients using the nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) genomic database. A total of 211 patients registered between June 2019 and March 2025 were analyzed. The most frequent genetic alterations were in BAP1, NF2, TP53, CDKN2A/B, and MTAP. The median tumor mutation burden (TMB) was 1.26, and no microsatellite instability–high patients were detected. The median overall survival (OS) after first-line treatment was 30.6 months. Patients treated with immune checkpoint inhibitors (ICIs) had a significantly better OS than those who did not receive ICIs. In univariate and multivariate analyses, TP53 alterations and high TMB (cutoff value of 1.6) were associated with poor prognosis. These results suggest that integrating clinical and genomic data can enhance prognostic stratification and contribute to the development of precision medicine for PM. This study provides the first large-scale genomic characterization of Japanese PM patients with C-CAT and highlights potential biomarkers for future therapeutic development.

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