Department 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.
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cell. 2018 Jan 11;172(1-2):205-217.e12. doi: 10.1016/j.cell.2017.12.007. Epub 2018 Jan 4.
Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing. Our data reveal a direct genomic lineage between in situ and invasive tumor subpopulations and further show that most mutations and copy number aberrations evolved within the ducts prior to invasion. These results support a multiclonal invasion model, in which one or more clones escape the ducts and migrate into the adjacent tissues to establish the invasive carcinomas.
导管原位癌（DCIS）是一种早期乳腺癌，很少进展为浸润性导管癌（IDC）。由于肿瘤内异质性和导管中肿瘤细胞数量少，侵袭过程中的基因组进化一直难以描绘。为了克服这些挑战，我们开发了拓扑单细胞测序（TSCS）技术，在保留组织切片中单肿瘤细胞空间背景的同时，测量其基因组拷贝数谱。我们对 10 名同时患有 DCIS 和 IDC 区域的患者的 1293 个单细胞进行了 TSCS 分析，此外还进行了外显子组测序。我们的数据揭示了原位和侵袭性肿瘤亚群之间的直接基因组谱系，并进一步表明，大多数突变和拷贝数异常是在侵袭前在导管内进化的。这些结果支持多克隆入侵模型，其中一个或多个克隆从导管逃逸并迁移到相邻组织中，从而建立侵袭性癌。
