Prevalence of PGVs in patients referred to a single clinical lab for germline genetic testing with an indication of uterine or endometrial cancer were retrospectively assessed and compared by syndrome type, patient age at testing, and self-reported ancestry. Potential clinical actionability of PGVs was based on established guidelines for clinical management, targeted therapies, and clinical trial eligibility.
PGVs were detected in 13.6% of the cohort (880/6490). PGVs were most frequently observed in Lynch syndrome genes (60.4%) and PTEN (1.5%), with 38.1% in another cancer predisposition gene (i.e., CHEK2, BRCA1/BRCA2). PGV prevalence was similar for patients <50 years and those ≥50 years (15.1% vs 13.2%). Nearly all PGVs (97.2%) were associated with guideline-recommended management, including cascade testing; 60.5% were associated with FDA-approved therapies; and 35.2% were associated with clinical trials.
Focusing germline testing on Lynch syndrome genes and PTEN and limiting testing to patients <50 years of age at diagnosis may overlook a substantial proportion of UC patients who harbor actionable PGVs. Universal comprehensive genetic testing of UC patients could benefit many patients and at-risk family members.
回顾性评估了在单一临床实验室进行生殖系基因检测的患者中PGV的患病率,并根据综合征类型进行了比较。患者年龄在测试,和自我报告的祖先。PGV的潜在临床可操作性是基于既定的临床管理指南,靶向治疗,和临床试验资格。
在13.6%的队列中检测到PGV(880/6490)。PGV在Lynch综合征基因(60.4%)和PTEN(1.5%)中最常见,在另一个癌症易感性基因中有38.1%(即,CHEK2,BRCA1/BRCA2)。<50岁和≥50岁患者的PGV患病率相似(15.1%vs13.2%)。几乎所有PGV(97.2%)都与指南推荐的管理相关,包括级联测试;60.5%与FDA批准的治疗相关;35.2%与临床试验相关.
将种系检测集中在Lynch综合征基因和PTEN上,并将检测限制在诊断时年龄<50岁的患者,可能会忽略相当大比例的携带可操作PGV的UC患者。UC患者的通用综合基因检测可以使许多患者和高危家庭成员受益。