继承性癌症的级联测试:综合的多基因面板在亲属中发现了意想不到的可操作的发现
Brandie Heald1, Sara Pirzadeh-Miller2, Rachel E Ellsworth1
1Medical Affairs, Invitae Corp, San Francisco, CA, USA.
Journal of the National Cancer Institute
|September 27, 2023
概括
目前针对家庭的癌症遗传测试指南可能错过了关键的发现. 在亲属的多基因小组测试中发现了意想不到的致病变体,导致癌症查和降低风险的机会被错过.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 医学诊断 医学诊断 医学诊断
背景情况:
- 目前的指导方针建议对已知癌症倾向基因变异的个体的亲属进行单个变异测试.
- 这种专注的方法可能会忽略其他基因中的致病变体,可能会推迟必要的癌症风险管理.
研究的目的:
- 评估基于多基因小组级联测试在癌症患者亲属中识别出意想不到的致病性生殖系变异的实用性.
- 确定这些意想不到的发现对癌症查建议的影响.
主要方法:
- 使用多基因面板进行了连锁测试,对来自7433名试验者的3696名亲属进行了测试.
- 分析的重点是识别致病或可能致病的生殖系变异,包括家族和非家族.
主要成果:
- 在6.2% (230) 的亲属中发现了意想不到的致病性或可能致病性生殖系变异.
- 其中,有144名亲属的基因变异与已知变异无关,而74人既有家族变异,也有额外的变异.
- 有意想不到变异的亲属中有36.3%有资格接受改变或额外的癌症查.
结论:
- 将级联测试仅限于家族变异的风险错过了可行的发现.
- 多基因小组测试为级联测试提供了更全面的方法,改善了可操作的生殖系变异的检测,并为癌症查策略提供了信息.
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