乳腺癌和相关克隆的进化史
Tomomi Nishimura1,2,3, Nobuyuki Kakiuchi1,4,5, Kenichi Yoshida1,6
1Department of Pathology and Tumour Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nature
|July 26, 2023
概括
乳腺癌的进化包括早期获得驱动突变,而非癌症克隆先于癌症克隆. 这项研究揭示了具有特定基因变异的乳腺癌的独特进化路径,
科学领域:
- 癌症学
- 遗传学
- 进化生物学
背景情况:
- 常见的癌症突变发生在正常组织中,在癌症发生之前.
- 早期克隆进化的驱动事件的序列和顺序在很大程度上是未知的.
- 了解乳腺癌的早期演变对于早期发现和预防至关重要.
研究的目的:
- 为了阐明乳腺癌的独特进化史与染色体变异.
- 确定乳腺癌发生的时间和顺序.
- 调查瘤内部异质性和癌症创始人的起源.
主要方法:
- 微切割癌症和非癌症病变的基因分析.
- 使用正常上皮细胞的突变率估计早期进化事件的时间.
- 对乳腺癌和AKT1突变病例的进化模式进行比较分析.
主要成果:
- 衍生性染色体der ((1;16) 在青春期获得,在30年代初之前具有共同的祖先.
- 癌症和非癌症克隆都是从这个共同的祖先进化出来的,而非癌症克隆是癌症之前的.
- 多个独立的癌症创始人经常来自非癌症祖先,导致瘤异质性.
- 驱动事件的数量与组织学无关,这表明微环境或表观遗传的影响.
结论:
- 乳腺癌的演变是一个多步骤的过程,涉及到正常组织中早期的驱动事件.
- 非癌症克隆可以作为多个独立的癌症创始人的前体.
- 这项研究为乳腺癌的进化轨迹提供了新的见解,
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