Edmondson Shelby, von Itzstein Mitchell S, Reys Brian, Mayer Melissa, Gagan Jeffrey, Gerber David E
UT Southwestern Medical School, Dallas, Texas.
Department of Internal Medicine (Division of Hematology-Oncology), University of Texas Southwestern Medical Center, Dallas, Texas.
JTO Clin Res Rep. 2022 Jun 25;3(8):100368. doi: 10.1016/j.jtocrr.2022.100368. eCollection 2022 Aug.
Heritable lung cancer may occur in the context of germline mutations (Li-Fraumeni syndrome). Limited cases of intrafamily tumor genomic characteristics have been reported.
A 40-year-old woman with no smoking history or known environmental exposure risk was incidentally found to have stage II (T2N1) NSCLC harboring an exon 19 p.Glu746_Ala750 deletion. Family history was notable for an identical twin sister with colorectal cancer (diagnosed at age 31 y) and a mother with stage I NSCLC harboring an exon 21 c.2573T>G (p.Leu858Arg) mutation (diagnosed at age 69 y). Genetic testing revealed a germline c.542G>A (p.Arg181His) mutation in the patient, her mother, and her sister, consistent with Li-Fraumeni syndrome. No germline mutations were detected.
Shared germline mutations may be associated with distinct NSCLC somatic mutations within families with Li-Fraumeni syndrome. Further understanding of the association between genetic cancer syndromes and lung cancer risk may improve early lung cancer detection in populations not otherwise meeting screening eligibility.
遗传性肺癌可能发生在种系突变（李-弗劳梅尼综合征）的背景下。关于家族内肿瘤基因组特征的病例报道有限。
主要关注点 重要临床发现 主要诊断 干预措施 结果：一名40岁女性，无吸烟史且无已知环境暴露风险，偶然发现患有II期（T2N1）非小细胞肺癌，伴有外显子19 p.Glu⁷⁴⁶_Ala⁷⁵⁰缺失。家族史值得注意的是，她有一个同卵双胞胎姐妹患结直肠癌（31岁时确诊），还有一位母亲患I期非小细胞肺癌，伴有外显子21 c.2573T>G（p.Leu⁸⁵⁸Arg）突变（69岁时确诊）。基因检测显示患者、其母亲和姐妹存在种系c.542G>A（p.Arg¹⁸¹His）突变，符合李-弗劳梅尼综合征。未检测到种系突变。
在李-弗劳梅尼综合征家族中，共享的种系突变可能与不同的非小细胞肺癌体细胞突变相关。进一步了解遗传性癌症综合征与肺癌风险之间的关联，可能会改善在其他不符合筛查条件人群中的早期肺癌检测。
