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

Our plain-English summary of Genomic landscape of pleural mesothelioma in Japanese patients: A comprehensive analysis using nationwide database, by H. Taniguchi, K. Akagi, T. Fukuda, et al (Translational Oncology, 2026).

The study

• Authors: H. Taniguchi, K. Akagi, T. Fukuda, T. Honda, H. Kurohama, N. Ueki, Y. Matsuoka, E. Udo, S. Yahata, S. Miura, H. Tomono, N. Honda, Y. Dotsu, M. Matsuo, S. Takemoto, I. Sato, S. Okano, M. Nakashima, H. Mukae, K. Ashizawa
• Journal: Translational Oncology
• Published: 2026;67:102731
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.

In plain English

This retrospective study used Japan's nationwide C-CAT database to describe pleural mesothelioma genetics. It covered 211 patients (151 men, 60 women; median age 68) tested from June 2019 to March 2025. Asbestos exposure was not recorded. The most common mutations were in BAP1, NF2, NOTCH3, TP53 and STK11, and the most common copy number changes in CDKN2A, CDKN2B, MTAP, BAP1 and TEK. Tumor mutation burden was low (median 1.26 mutations per megabase), with no microsatellite instability-high tumors. Median overall survival from first-line treatment was 30.6 months (95% confidence interval 24.1 to 40.2). Patients given immune checkpoint inhibitors had longer median survival than those not given them (31.0 months, 95% CI 26.0 to 40.9, vs 12.9 months, 95% CI 10.5 to not available), though the authors noted few went without them. TP53 alterations and tumor mutation burden of 1.6 mutations per megabase or higher were associated with shorter survival. The pattern was largely consistent with mainly Western TCGA data. The authors concluded that several factors may be useful biomarkers, and cited retrospective design, possible selection bias and small sample size as limitations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective nationwide cohort study of a clinical-genomic database (C-CAT), with comparison to publicly available TCGA mesothelioma data
• Who was studied: 211 patients with pleural mesothelioma in Japan who underwent comprehensive genomic profiling between June 2019 and March 2025 and were registered in the C-CAT database; 151 males and 60 females, median age 68 years
• Exposure: The study examined tumor genetic alterations, tumor mutation burden and treatment (including immune checkpoint inhibitors), not asbestos. Asbestos exposure history was not recorded in the database.
• Main results:
  • The most frequent gene mutations in the C-CAT cohort were in BAP1, NF2, NOTCH3, TP53 and STK11.
  • The most frequent copy number changes were in CDKN2A, CDKN2B, MTAP, BAP1 and TEK.
  • No microsatellite instability-high patients were found. Median tumor mutation burden was 1.26 (measured in mutations per megabase), and only five patients had 10 or more mutations per megabase.
  • No cases with germline BAP1 alterations were found in the database.
  • Compared with TCGA data (mainly Western populations), the overall pattern of alterations was largely consistent; differences in the gene spectrum were not statistically significant.
  • Median overall survival from the start of first-line therapy for the whole cohort was 30.6 months (95% CI, 24.1 to 40.2).
  • Patients who received immune checkpoint inhibitors had longer survival than those who did not: 31.0 months (95% CI, 26.0 to 40.9) vs 12.9 months (95% CI, 10.5 to not available), p = 0.012. 186 patients received ICIs at some point and 15 did not.
  • There was no statistically significant survival difference between epithelioid and non-epithelioid subtypes. There was a trend toward longer survival in the epithelioid group: 32.5 vs 24.9 months.
  • TMB-high was defined as 1.6 mutations per megabase or more. Survival was longer in the TMB-low group than the TMB-high group: 42.0 months (95% CI, 28.4 to not available) vs 23.4 months (95% CI, 17.7 to 32.3), p = 0.00064.
  • Survival was shorter in patients with TP53 mutations than in those without: 15.2 months (95% CI, 13.4 to 35.7) vs 32.3 months (95% CI, 29.4 to 43.7).
  • Survival was shorter in patients with CDKN2A alterations than in those without: 28.4 months (95% CI, 22.3 to 36.7) vs 36.0 months (95% CI, 24.1 to 62.3).
  • Alterations in BAP1, NF2, CDKN2B and MTAP were not significantly associated with survival.
  • In multivariate analysis, performance status 0 was a favorable prognostic factor. High TMB and alterations in TP53, MST1R and CDKN2A were associated with poor prognosis.
• The authors' conclusion: The authors concluded that, although alterations directly targetable by existing drugs are limited, several factors may be clinically relevant biomarkers, and that combining clinical and genomic information may help predict outcomes.
• Limitations the authors state:
  • The study was a retrospective database analysis, with potentially incomplete clinical data and delayed survival updates.
  • There is a risk of selection bias in which patients underwent genomic testing.
  • The targeted sequencing tests provide less genomic coverage than whole-exome or transcriptomic analyses.
  • Information on surgery and radiation was not available.
  • Clonal hematopoiesis and comprehensive gene co-alterations could not be evaluated.
  • The sample size was relatively small, so analyses such as propensity score matching could not be done.
  • Few patients did not receive immune checkpoint inhibitors, so the comparisons by ICI use should be interpreted cautiously.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, BAP1, CDKN2A, MTAP, Microsatellite Instability (MSI-H), Median Overall Survival, checkpoint inhibitors, Prognosis.

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