Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.
Department of Public Health, University Federico II of Naples, Naples, Italy.
J Thorac Oncol. 2023 Sep;18(9):1146-1164. doi: 10.1016/j.jtho.2023.05.028. Epub 2023 Jun 16.
Considering the established contribution of environmental factors to the development of thoracic malignancies, the inherited susceptibility of these tumors has rarely been explored. However, the recent introduction of next-generation sequencing-based tumor molecular profiling in the real-word setting enabled us to deeply characterize the genomic background of patients with lung cancer with or without smoking-related history, increasing the likelihood of detecting germline mutations with potential prevention and treatment implications. Pathogenic germline variants have been detected in 2% to 3% of patients with NSCLC undergoing next-generation sequencing analysis, whereas the proportion of germline mutations associated with the development of pleural mesothelioma widely varies across different studies, ranging between 5% and 10%. This review provides an updated summary of emerging evidence about germline mutations in thoracic malignancies, focusing on pathogenetic mechanisms, clinical features, therapeutic implications, and screening recommendations for high-risk individuals.
考虑到环境因素对胸内恶性肿瘤发展的既定贡献，这些肿瘤的遗传易感性很少被探索。然而，最近在实际环境中引入基于下一代测序的肿瘤分子谱分析，使我们能够深入描述有或无吸烟相关史的肺癌患者的基因组背景，增加了检测具有潜在预防和治疗意义的种系突变的可能性。在接受下一代测序分析的 NSCLC 患者中，检测到 2%至 3%的致病性种系变体，而与胸膜间皮瘤发展相关的种系突变的比例在不同研究中差异很大，范围在 5%至 10%之间。本综述提供了关于胸内恶性肿瘤中种系突变的最新证据总结，重点介绍了发病机制、临床特征、治疗意义以及高危人群的筛查建议。
