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档案单细胞基因组学揭示了DCIS进展期间的持续子克隆
Kaile Wang1, Tapsi Kumar2, Junke Wang3
1Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genetics, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
Cell
|August 16, 2023
概括
一种新的单细胞DNA测序方法,Arc-well,分析了固定在甲中的瘤样本. 这种方法揭示了管道内癌 (DCIS) 经常具有基因组变化和与复发性癌症的共同血统.
科学领域:
- 基因组学
- 癌症生物学
- 分子病理学
背景情况:
- 在位管道癌 (DCIS) 是侵袭性乳腺癌的前体,但其基因组进展到复发是不清楚的.
- 在临床环境中常见的甲固定嵌 (FFPE) 组织的基因组分析存在重大挑战.
研究的目的:
- 开发和验证与FFPE材料兼容的高通量单细胞DNA测序方法.
- 调查DCIS的基因组景观和进化轨迹及其进展到复发性疾病.
主要方法:
- 开发Arc-well,一种用于FFPE样本的新型单细胞DNA测序技术.
- 从细胞系,冷组织和27个FFPE瘤样本 (乳腺,肺,前列腺) 进行了40330个单细胞的分析,存储时间为3至31年.
- 对10名患者的DCIS和复发癌症样本进行基因组比较分析.
主要成果:
- 通过Arc-well成功地从老化的FFPE样本中分析单细胞.
- 许多DCIS初级样本表现出全基因组翻倍和克隆多样化.
- 在复发性癌症中,原发性DCIS和持久性亚克隆之间共享基因谱.
- 在大多数DCIS病例中观察到进化瓶,与复发相关的特定染色体异常.
结论:
- 弧井是一种可行的FFPE组织单细胞基因组分析方法.
- 早期的DCIS具有显著的基因组异质性和进化潜力.
- 了解DCIS的基因组演变对于预测和预防癌症复发至关重要.
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