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宪法BRCA1表皮转移:了解基底性乳腺癌和高度血清性卵巢癌的关键
Per E Lønning1, Oleksii Nikolaienko1,2, Stian Knappskog1,2
1K.G. Jebsen Center for Genome-Directed Cancer Therapy Department of Oncology Haukeland University Hospital, Bergen, Norway.
Human mutation
|April 14, 2025
概括
白细胞中的马赛克BRCA1表皮突变显著增加了三阴性乳腺癌和卵巢癌的风险. 这些早期胚胎事件导致大约20%的三阴性乳腺癌.
科学领域:
- 遗传学 遗传学 是一个
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 在BRCA1和BRCA2基因中的生殖系致病变体是遗传性乳腺和卵巢癌的主要原因.
- 在三阴性乳腺癌 (TNBC) 和高度血清性卵巢癌 (HGSOC) 组织中经常发现BRCA1表皮.
- 之前的研究表明BRCA1表皮突变与癌症风险之间存在关联,但并没有正式评估危险比率.
研究的目的:
- 评估与白细胞 (WBC) 中的马赛克BRCA1表皮突变相关的发生TNBC和HGSOC的危险比率.
- 确定由BRCA1表皮突变引起的TNBC病例的比例.
- 调查BRCA1表皮突变的时间和起源.
主要方法:
- 在妇女健康倡议研究中进行的前性嵌套病例控制研究.
- 在WBC和TNBC患者的瘤样本中分析BRCA1表皮.
- 在各种组织和新生儿中评估BRCA1表皮突变.
主要成果:
- 马赛克WBC BRCA1表皮,即使在低等位基因频率 (<0.1%),显著增加发生HGSOC和TNBC的风险超过5年.
- 鉴定出BRCA1表皮突变是大约20%的TNBC病例的原因,超过了生殖系BRCA1变异的发生率.
- 在所有三个生殖层中检测到主要的宪法BRCA1表皮,在WBC,正常和瘤乳腺组织中存在相同的等位基因,这表明早期的胚胎起源.
结论:
- 在WBC中马赛克BRCA1表皮图是TNBC和HGSOC的重要危险因素.
- BRCA1表皮突变代表了TNBC的一个实质性原因,独立于生殖系突变.
- 证据强烈表明,BRCA1表皮突变是由早期胚胎事件引起的,随后的克隆扩张影响了所有胚胎层.
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