PDF(Pubmed)
Abstract：
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 (10 ATM, 8 BRCA2, and 3 BRCA1). 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：
在非小细胞肺癌（NSCLC）患者中，致病性种系变体（PGV）可能未被检测为病因。据报道，PGV的患病率在1％至15％的患者之间，取决于患者群体。西班牙裔/拉丁裔人口中的比率仍然未知。我们回顾性分析了基因组结果(Guardant360，红木城，CA,美国）南佛罗里达州五个中心的878例晚期或转移性NSCLC患者，美国,从2019年到2022年，分析通过循环无细胞肿瘤DNA（ctDNA）鉴定的附带PGV（iPGV）的比率。然后我们根据肿瘤组织学对结果进行分层，年龄,性别,种族,种族,遗传途径,和共同突变。鉴定出21个iPGV(21/878=2.4%)。在确定的21个iPGV中，女性14例（66.7%），男性7例（33.3%）。中位年龄为67岁，烟草史为2.5包年。总的来说,52.4％的患者被确定为任何种族的西班牙裔/拉丁裔（n=11）；19.0％为Ashkenazi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)。同源重组修复途径中的iPGV仅在该队列中表达（10ATM，8BRCA2和3BRCA1)。总的来说,76%(16/21)的iPGV患者共表达体细胞改变，56%(9/16)的人证明了可靶向基因的改变。总的来说,我们的实际发现提供了不同人群NSCLC患者中iPGV的点患病率,例如报告西班牙裔/拉丁裔的患者。
