从未吸烟的巴西患者肺腺癌驱动基因的分子谱：对靶向治疗的影响。
Molecular profile of driver genes in lung adenocarcinomas of Brazilian patients who have never smoked: implications for targeted therapies.
发表日期：2024 Jun 29
作者：
Rodrigo de Oliveira Cavagna, Flávia Escremim de Paula, Gustavo Noriz Berardinelli, Murilo Bonatelli, Iara Santana, Eduardo Caetano Albino da Silva, Gustavo Ramos Teixeira, Beatriz Garbe Zaniolo, Josiane Mourão Dias, Flávio Augusto Ferreira da Silva, Carlos Eduardo Baston Silva, Marcela Gondim Borges Guimarães, Camila Pinto Barone, Alexandre Arthur Jacinto, Rachid Eduardo Noleto da Nóbrega Oliveira, José Elias Miziara, Pedro De Marchi, Miguel A Molina-Vila, Letícia Ferro Leal, Rui Manuel Reis
来源：
MOLECULAR & CELLULAR PROTEOMICS
摘要：
从不吸烟者 (LCINS) 患者患的肺癌占肺癌病例的 20%，其生物学特性仍然知之甚少，尤其是在基因混合人群中。我们阐明了巴西 LCINS 中驱动基因的分子谱。使用靶向测序 (NGS)、nCounter 和免疫组织化学评估了来自自我报告的从不吸烟患者的 119 例肺腺癌的突变和基因融合状态。一组 46 个祖先信息标记确定了患者的遗传祖先。最常见的突变基因是 EGFR (49.6%)，其次是 TP53 (39.5%)、ALK (12.6%)、ERBB2 (7.6%)、KRAS (5.9%) )、PIK3CA (1.7%)，以及 RET、NTRK1、METΔex14、PDGFRA 和 BRAF 的变化小于 1%。除TP53和PIK3CA外，所有其他改变都是相互排斥的。遗传血统分析显示，欧洲血统占主导地位（71.1%），较高的非洲血统与 TP53 突变相关。除了 ALK 和 TP53 改变增加外，巴西 LCINS 表现出与其他人群相似的分子特征。重要的是，其中 73% 的患者有适合针对性治疗的可行改变。© 作者 2024。由牛津大学出版社出版。
Lung cancer in never-smoker (LCINS) patients accounts for 20% of lung cancer cases, and its biology remains poorly understood, particularly in genetically admixed populations. We elucidated the molecular profile of driver genes in Brazilian LCINS.The mutational and gene fusion status of 119 lung adenocarcinomas from self-reported never-smoker patients, was assessed using targeted sequencing (NGS), nCounter, and immunohistochemistry. A panel of 46 ancestry-informative markers determined patients' genetic ancestry.The most frequently mutated gene was EGFR (49.6%), followed by TP53 (39.5%), ALK (12.6%), ERBB2 (7.6%), KRAS (5.9%), PIK3CA (1.7%), and less than 1% alterations in RET, NTRK1, MET∆ex14, PDGFRA, and BRAF. Except for TP53 and PIK3CA, all other alterations were mutually exclusive. Genetic ancestry analysis revealed a predominance of European (71.1%), and a higher African ancestry was associated with TP53 mutations.Brazilian LCINS exhibited a similar molecular profile to other populations, except the increased ALK and TP53 alterations. Importantly, 73% of these patients have actionable alterations that are suitable for targeted treatments.© The Author(s) 2024. Published by Oxford University Press.