致命的转移性前列腺癌的进化历史
Gunes Gundem1, Peter Van Loo1,2,3, Barbara Kremeyer1
1Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Nature
|April 2, 2015
概括
转移可以通过多个癌细胞克隆传播,而不是一个. 这项研究揭示了复杂的转移模式,并告知前列腺癌的治疗耐药性.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 进化医学是一种进化医学.
背景情况:
- 癌症进化涉及达尔文选择,导致瘤亚克隆.
- 转移形成导致90%的癌症死亡,但传播原理不明.
- 多克隆播种 (多个克隆) 和克隆间合作是由小鼠模型提出的.
研究的目的:
- 提供人类癌症中多克隆播种的最终证据.
- 研究前列腺癌转移中的克隆关系.
- 了解转移的传播和对抗雄激素缺乏治疗的耐药性.
主要方法:
- 从十名前列腺癌患者的原发性瘤和多重转移的全基因组测序.
- 对亚克隆架构的综合分析,以绘制转移性传播模式.
- 在瘤抑制基因和雄激素受体信号通路基因的遗传变化的表征.
主要成果:
- 从转移到转移的传播很常见,涉及单克隆播种和多克隆转移多个克隆.
- 五个病例显示了多个瘤克隆在转移性部位之间转移的证据.
- 瘤抑制基因病变通常以单一事件的形式出现,而雄激素受体路径突变显示出横跨转移的融合进化.
结论:
- 人类恶性瘤表现出多克隆播种,挑战了单细胞起源假说.
- 阐明了复杂的转移模式,包括转移间传播.
- 这些发现有助于更好地了解前列腺癌的进展和对抗雄激素缺乏治疗的抵抗力.
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