Prognostic impact of somatic mutations among patients with pleural and peritoneal mesothelioma
The study demonstrates that truncating NF2 mutations, along with mutations in CDKN2A and TERT, are independently associated with worse overall survival in pleural mesothelioma, underscoring the prognostic significance of specific somatic mutations and supporting biomarker‑guided trial enrollment and targeted therapy development.
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‑month (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.
Understanding how specific somatic mutations influence prognosis in pleural and peritoneal mesothelioma can help clinicians stratify patients for appropriate therapies and guide future clinical trial design, ultimately aiming to improve patient outcomes.
Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.
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