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通过拓单细胞测序识别乳腺瘤的多细胞侵袭
Anna K Casasent1, Aislyn Schalck1, Ruli Gao2
1Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cell
|January 9, 2018
概括
拓单细胞测序 (TSCS) 揭示了乳腺癌在发病之前的早期发展. 大多数基因组变化发生在入侵前的管道内,支持多克隆入侵模型.
科学领域:
- 癌症学
- 基因组学
- 癌症生物学
背景情况:
- 在位管道癌 (DCIS) 是乳腺癌的早期阶段.
- 由于研究瘤演变的挑战,从DCIS发展为侵袭性导管癌 (IDC) 尚不完全理解.
- 瘤内异质性和有限的瘤细胞数量使基因组分析复杂化.
研究的目的:
- 开发和应用一种用于分析单个瘤细胞在它们的空间环境中的基因组变化的新方法.
- 将乳腺癌的基因组演变从现场到侵袭性阶段进行划分.
- 研究DCIS和IDC种群之间的克隆关系.
主要方法:
- 拓单细胞测序 (TSCS) 的开发,以分析单个瘤细胞拷贝数的变化.
- 在组织段内保存单个瘤细胞的空间背景.
- 用TSCS对来自10名同步DCIS和IDC患者的1,293个单细胞进行测序,并通过外体测序进行补充.
主要成果:
- 在保持空间信息的同时,TSCS成功测量了单个瘤细胞的基因组复制量.
- 在现场和侵袭性瘤亚群之间确定了直接的基因组系.
- 大多数突变和拷贝数异常都是在入侵前进化的.
结论:
- 这项研究提供了直接的基因组证据,将管道癌与侵袭性管道癌联系起来.
- 基因组进化,包括突变和拷贝数异常,在很大程度上先于侵入性过程.
- 这些发现支持一种多克隆入侵模型,预先进化的克隆从导管中传播,形成侵入性癌症.
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