生物
计算生物学
显微解剖
导管癌
基因组学
基因组
转录组
原位
DNA测序
激光捕获显微切割
癌症
单细胞测序
癌症的体细胞进化
克隆(Java方法)
进化生物学
遗传学
乳腺癌
基因
外显子组测序
基因表达
物理
气象学
突变
作者
Artem Lomakin,Jessica Svedlund,Carina Strell,Milana Gatarić,Artem Shmatko,Gleb D. Rukhovich,Jun Sung Park,Young Seok Ju,Stefan C. Dentro,Vitalii Kleshchevnikov,Vasyl Vaskivskyi,Tong Li,Omer Ali Bayraktar,Sarah Pinder,Andrea L. Richardson,Sandro Santagata,Peter J. Campbell,Hege G. Russnes,Moritz Gerstung,Mats Nilsson,Lucy R. Yates
出处
期刊:Nature
[Springer Nature]
日期:2022-11-09
卷期号:611 (7936): 594-602
被引量:53
标识
DOI:10.1038/s41586-022-05425-2
摘要
Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour1-3. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive4,5. Here, to address this need, we developed a workflow that generates detailed quantitative maps of genetic subclone composition across whole-tumour sections. These provide the basis for studying clonal growth patterns, and the histological characteristics, microanatomy and microenvironmental composition of each clone. The approach rests on whole-genome sequencing, followed by highly multiplexed base-specific in situ sequencing, single-cell resolved transcriptomics and dedicated algorithms to link these layers. Applying the base-specific in situ sequencing workflow to eight tissue sections from two multifocal primary breast cancers revealed intricate subclonal growth patterns that were validated by microdissection. In a case of ductal carcinoma in situ, polyclonal neoplastic expansions occurred at the macroscopic scale but segregated within microanatomical structures. Across the stages of ductal carcinoma in situ, invasive cancer and lymph node metastasis, subclone territories are shown to exhibit distinct transcriptional and histological features and cellular microenvironments. These results provide examples of the benefits afforded by spatial genomics for deciphering the mechanisms underlying cancer evolution and microenvironmental ecology.
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