条形码揭示了新转变的人类乳腺细胞复杂的克隆动态
Long V Nguyen1, Davide Pellacani1,2, Sylvain Lefort1
1Terry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
Nature
|December 4, 2015
概括
在小鼠中迅速形成侵袭性乳腺癌. 这挑战了癌症发展需要多个突变的观点,
科学领域:
- 癌症学
- 遗传学
- 细胞生物学
背景情况:
- 人类乳腺癌的异质性使得了解早期致癌事件变得复杂.
- 乳腺癌的细胞起源和最初的遗传变化仍然具有挑战性.
研究的目的:
- 研究人类乳腺癌起源的早期事件.
- 描述正常乳腺细胞的细胞背景和癌基因驱动的转变.
- 挑战现有的致癌模式,
主要方法:
- 用KRAS ((G12D)) 瘤基因从正常的人类乳腺组织中分离和转导基底细胞和光原体.
- 在免疫缺陷小鼠体内植入上和皮下以产生瘤.
- 用于克隆分析和转录瘤的DNA条形码.
主要成果:
- 在8周内,转移的基底细胞和光原体迅速形成了可连续移植的多克隆性侵入性导管癌.
- DNA 条形码检测显示,在 2 周内显著的克隆进化和新克隆的出现以及连续传递的瘤.
- 主要瘤表现出表型异质性,并被转录分类为"正常类型".
结论:
- 一个单独的瘤基因可以从正常的人类乳腺上皮细胞开始快速形成乳腺癌,从而挑战多个突变的必要性.
- 该模型提供了对恶性转变的初始事件和人类乳腺癌异质性的快速发展的见解.
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