患有肺癌的患者中致病性生殖系变异的比率
Steven Sorscher1, Jaclyn LoPiccolo2, Brandie Heald1
1Invitae, San Francisco, CA.
JCO precision oncology
|November 22, 2023
概括
肺癌 (LC) 患者的生殖系基因检测显示了致病性生殖系变体 (PGV) 的高频率,特别是在DNA损伤修复基因中. 这些发现支持对肺癌的更广泛的GGT建议.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 胚胎基因检测 (GGT) 是几种癌症的标准,但对于肺癌 (LC) 并不是普遍的.
- 在LC患者中缺乏关于致病性生殖系变体 (PGV) 频率的证据,阻碍了GGT建议.
- 这项研究研究了GGT在多样化的LC队列中的结果.
研究的目的:
- 在被诊断为肺癌的患者中描述PGV的频率和频谱.
- 为了比较LC患者和对照人群中的PGV率.
- 分析不同基因组祖先和癌症史上的PGV患病率.
主要方法:
- 从7788名LC患者 (2015-2022) 获得的非识别的GGT数据的回顾性分析.
- 将PGV频率与未受影响个体的对照队列进行比较.
- 根据基因组祖先,个人/家庭癌症史以及临床可行性,对GGT结果的分层.
主要成果:
- 14.9%的LC患者患有PGV,即使没有其他癌症的个人或家族病史,这一比例也是一致的.
- 与对照组相比,PGVs在BRCA2,ATM,CHEK2,BRCA1和不匹配修复基因中得到显著丰富.
- 欧洲祖先的PGV率最高 (18%);61.3%的PGV在DNA损伤修复基因中,95%是临床可行的.
结论:
- 肺癌诊断与在祖先之间潜藏致癌PGVs的显著可能性有关.
- 在DNA损伤修复基因中PGVs的丰富表明在肺癌倾向中发挥作用.
- 肺癌患者的GGT确定了可操作的变体,支持扩大测试建议.
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