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<p>Mesothelioma is a rare cancer with poor prognosis. Somatic mutations show prognostic value in smaller studies; however, detailed survival analysis of mutations, specific variants, and co-mutations are unknown. This study gathered one of the largest mesothelioma cohorts in North America to determine prognostic impact of treatments, tumor characteristics, and somatic mutations. Among 195 patients, 70% (n = 137) had pleural and 30% (n = 58) had peritoneal mesothelioma. <i>NF2</i>, <i>TERT</i>, and <i>CDKN2A</i> had worse OS in pleural mesothelioma. <i>NF2</i> mutations with truncated NF2 protein (non-sense and frameshift with premature stop codon) had worse OS in pleural mesothelioma (log-rank-p &lt; 0.001). Conversely, <i>NF2</i> pathogenic mutations with loss-of-function/structural variants were <i>not</i> associated with OS, revealing that <i>NF2</i> truncating mutations may drive <i>NF2</i>’s prognostic impact. This is emphasized by higher mortality at 1-year (44% vs 7.7%, p = 0.044) and 18-months (69% vs 17%, p = 0.006) compared to non-truncating <i>NF2</i> mutations. Overall, this study found that pleural and peritoneal mesothelioma have unique mutations with prognostic significance. Furthermore, as trials demonstrate varied results in <i>NF2</i>-targeted treatments, this study supports biomarker-informed strategies to guide trial enrollment and development of targeted-therapies.</p>

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Prognostic impact of somatic mutations among patients with pleural and peritoneal mesothelioma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Justin M. Bader,
  • Ankit Dhiman,
  • Nicole Aguirre,
  • Kwasi Ansere Ofori,
  • Princy Gupta,
  • Hannah Qin,
  • Anup Sharma,
  • Owen Mitchell,
  • Melissa Y. Tjota,
  • Aliya N. Husain,
  • Michael Drazer,
  • Jane Churpek,
  • Hedy Kindler,
  • Kiran Turaga

摘要

Mesothelioma is a rare cancer with poor prognosis. Somatic mutations show prognostic value in smaller studies; however, detailed survival analysis of mutations, specific variants, and co-mutations are unknown. This study gathered one of the largest mesothelioma cohorts in North America to determine prognostic impact of treatments, tumor characteristics, and somatic mutations. Among 195 patients, 70% (n = 137) had pleural and 30% (n = 58) had peritoneal mesothelioma. NF2, TERT, and CDKN2A had worse OS in pleural mesothelioma. NF2 mutations with truncated NF2 protein (non-sense and frameshift with premature stop codon) had worse OS in pleural mesothelioma (log-rank-p < 0.001). Conversely, NF2 pathogenic mutations with loss-of-function/structural variants were not associated with OS, revealing that NF2 truncating mutations may drive NF2’s prognostic impact. This is emphasized by higher mortality at 1-year (44% vs 7.7%, p = 0.044) and 18-months (69% vs 17%, p = 0.006) compared to non-truncating NF2 mutations. Overall, this study found that pleural and peritoneal mesothelioma have unique mutations with prognostic significance. Furthermore, as trials demonstrate varied results in NF2-targeted treatments, this study supports biomarker-informed strategies to guide trial enrollment and development of targeted-therapies.