Spatial genomics maps the structure, nature and evolution of cancer clones.
Spatial genomics maps the structure, nature and evolution of cancer clones.
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DOI：
10.1038/s41586-022-05425-2
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发表时间：
2022-11
期刊：
影响因子：
64.8
通讯作者：
Yates, Lucy R.
中科院分区：
文献类型：
--
作者：
Lomakin, Artem;Svedlund, Jessica;Strell, Carina;Gataric, Milana;Shmatko, Artem;Rukhovich, Gleb;Park, Jun Sung;Ju, Young Seok;Dentro, Stefan;Kleshchevnikov, Vitalii;Vaskivskyi, Vasyl;Li, Tong;Bayraktar, Omer Ali;Pinder, Sarah;Richardson, Andrea L.;Santagata, Sandro;Campbell, Peter J.;Russnes, Hege;Gerstung, Moritz;Nilsson, Mats;Yates, Lucy R.
癌症的基因组测序经常揭示同一肿瘤中存在的不同亚克隆的嵌合体。虽然这些被认为是根据体细胞进化的原则，确切的空间生长模式和潜在的机制仍然难以捉摸。在这里，为了满足这一需求，我们开发了一个工作流程，可以生成整个肿瘤切片中遗传亚克隆组成的详细定量图谱。这些为研究克隆生长模式、克隆的组织学特征、显微解剖和微环境组成提供了基础。该方法依赖于全基因组测序，然后是高度多路复用的碱基特异性原位测序，单细胞分辨转录组学和连接这些层的专用算法。将碱基特异性原位测序工作流程应用于来自两个多灶性原发性乳腺癌的八个组织切片，揭示了通过显微切割验证的复杂亚克隆生长模式。在导管原位癌的情况下，多克隆肿瘤扩张发生在宏观尺度上，但在显微解剖结构内隔离。在导管原位癌、浸润性癌和淋巴结转移的各个阶段，亚克隆区域显示出不同的转录和组织学特征以及细胞微环境。这些结果提供了空间基因组学的好处，破译癌症演变和微环境生态学的机制的例子。以碱基特异性原位测序为中心的工作流程可以生成癌症亚克隆独特集的详细图谱，并可以对其进行表型表征。
Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive. 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. A workflow centred around base-specific in situ sequencing generates detailed maps of, and can phenotypically characterize, the unique set of subclones of cancers.
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影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
DOI：
10.1073/pnas.0712345105
发表时间：
2008-03-18
影响因子：
11.1
作者：
Jones, Sian;Chen, Wei-dong;Markowitz, Sanford D.
通讯作者：
Markowitz, Sanford D.
影响因子：
82.9
作者：
Andor N;Graham TA;Jansen M;Xia LC;Aktipis CA;Petritsch C;Ji HP;Maley CC
通讯作者：
Maley CC
影响因子：
14.8
作者：
Ellis, Peter;Moore, Luiza;Campbell, Peter J.
通讯作者：
Campbell, Peter J.
影响因子：
0.5
作者：
DOBZHANSKY, T
通讯作者：
DOBZHANSKY, T