通过线粒体突变追踪人类肿瘤细胞谱系

Tracing of Human Tumor Cell Lineages by Mitochondrial Mutations.

作者信息

Refinetti Paulo, Morgenthaler Stephan, Thilly William G, Arstad Christian, Ekstrøm Per O

机构信息

Chair of Applied Statistics, Mathematics Section, School of Basic Sciences, École Polytechnique Fédéral de Lausanne (EPFL), Lausanne, Switzerland.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States.

出版信息

Front Oncol. 2020 Dec 3;10:523860. doi: 10.3389/fonc.2020.523860. eCollection 2020.

DOI:10.3389/fonc.2020.523860

PMID:33344219

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7745703/

Abstract

BACKGROUND

Previous studies have shown the value in studying lineage tracing in slices of human tumors. However, a tumor is not a two-dimensional structure and to better understand how a tumor, and its corresponding metastasis grow, a three-dimensional (3-D) view is necessary.

RESULTS

Using somatic mitochondrial mutations as a marker for lineage tracing, it is possible to identify and follow tumor specific cell lineages. Using cycling temperature capillary electrophoresis (CTCE) a total of 8 tissues from 5 patients (4 primary tumors and 4 metastasis) containing clear mitochondrial markers of tumor lineages were selected. From these 8 tissues over 9,500 laser capture microdisection (LCM) samples were taken and analyzed, in a way that allows 3-D rendering of the observations.

CONCLUSION

Using CTCE combined with LCM makes it possible to study the 3-D patterns formed by tumors and metastasis as they grow. These results clearly show that the majority of the volume occupied by a tumor is not composed of tumor derived cells. These cells are most likely recruited from the neighboring tissue.

摘要

背景

先前的研究已表明在人类肿瘤切片中进行谱系追踪研究的价值。然而，肿瘤并非二维结构，为了更好地理解肿瘤及其相应转移灶的生长方式，三维（3-D）视角是必要的。

结果

利用体细胞线粒体突变作为谱系追踪的标记，能够识别并追踪肿瘤特异性细胞谱系。使用循环温度毛细管电泳（CTCE），从5名患者的总共8个组织（4个原发性肿瘤和4个转移灶）中选取了含有明确肿瘤谱系线粒体标记的组织。从这8个组织中采集并分析了超过9500个激光捕获显微切割（LCM）样本，其方式能够对观察结果进行三维呈现。