文章：

在主要西班牙裔/拉丁裔人群中，非小细胞肺癌患者通过循环肿瘤DNA检测发现的偶发性致病性胚系突变特征分析

Characterization of Incidental Pathogenic Germline Findings Detected via ctDNA among Patients with Non-Small Cell Lung Cancer in a Predominantly Hispanic/Latinx Population

原文发布日期：14 March 2024

DOI: 10.3390/cancers16061150

类型: Article

开放获取: 是

英文摘要：

Pathogenic germline variants (PGVs) may be under-detected as causative etiologies in patients with non-small cell lung cancer (NSCLC). The prevalence of PGVs has been reported between 1 and 15% of patients, depending on the patient population. The rate within Hispanic/Latinx populations remains unknown. We retrospectively analyzed the genomic results (Guardant360, Redwood City, CA, USA) of 878 patients with advanced or metastatic NSCLC at five centers in South Florida, USA, from 2019 to 2022 to analyze the rate of incidental PGVs (iPGVs) identified via circulating cell-free tumor DNA (ctDNA). We then stratified the results by tumor histology, age, gender, race, ethnicity, genetic pathway, and co-mutations. Twenty-one iPGVs were identified (21/878 = 2.4%). Among the 21 iPGVs identified, 14 patients were female (66.7%) and 7 were male (33.3%), with a median age of 67 years and tobacco history of 2.5 pack-years. In total, 52.4% of patients identified as Hispanic/Latinx (n= 11) of any race; 19.0% as Ashkenazi Jewish (n= 4), 9.5% as non-Hispanic/Latinx black (n= 2), and 19.0% as non-Hispanic/Latinx white (n= 4). iPGVs in the homologous recombination repair pathway were solely expressed in this cohort (10ATM, 8BRCA2, and 3BRCA1). In total, 76% (16/21) of patients with iPGVs co-expressed somatic alterations, with 56% (9/16) demonstrating alterations in targetable genes. Overall, our real-world findings offer a point prevalence of iPGVs in patients with NSCLC of diverse populations, such as patients who report Hispanic/Latinx ethnicity.

摘要翻译： 

致病性胚系变异（PGVs）在非小细胞肺癌（NSCLC）患者中作为病因可能未被充分检出。据文献报道，PGVs的检出率在1%至15%之间，具体取决于患者群体特征。而在西班牙裔/拉丁裔人群中的发生率仍属未知。本研究回顾性分析了2019年至2022年间美国南佛罗里达州五个医疗中心878例晚期或转移性NSCLC患者的基因组检测结果（采用Guardant360检测平台，美国加州雷德伍德城），通过循环肿瘤游离DNA（ctDNA）检测分析偶然发现的PGVs（iPGVs）发生率，并按肿瘤组织学类型、年龄、性别、种族、民族、遗传通路及共突变情况进行分层分析。共检出21例iPGVs（21/878=2.4%），其中女性14例（66.7%）、男性7例（33.3%），中位年龄67岁，中位吸烟史为2.5包年。按民族分类：52.4%的患者为西班牙裔/拉丁裔（n=11），19.0%为德系犹太人（n=4），9.5%为非西班牙裔/拉丁裔黑人（n=2），19.0%为非西班牙裔/拉丁裔白人（n=4）。所有iPGVs均出现在同源重组修复通路（10例ATM、8例BRCA2、3例BRCA1）。76%（16/21）的iPGVs患者同时存在体细胞突变，其中56%（9/16）的突变位于可靶向基因。本研究通过真实世界数据，首次揭示了包含西班牙裔/拉丁裔人群在内的多民族NSCLC患者群体中iPGVs的现患率特征。

原文链接：

Characterization of Incidental Pathogenic Germline Findings Detected via ctDNA among Patients with Non-Small Cell Lung Cancer in a Predominantly Hispanic/Latinx Population