Tracing of Human Tumor Cell Lineages by Mitochondrial Mutations

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

doi:10.3389/fonc.2020.523860

Tracing of Human Tumor Cell Lineages by Mitochondrial Mutations

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

Authors

Paulo Refinetti¹, Stephan Morgenthaler¹, William G Thilly², Christian Arstad³, Per O Ekstrøm³

Affiliations

¹ Chair of Applied Statistics, Mathematics Section, School of Basic Sciences, École Polytechnique Fédéral de Lausanne (EPFL), Lausanne, Switzerland.
² Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States.
³ Department of Tumor Biology, Norwegian Radium Hospital, Oslo, Norway.

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.

Keywords: human; lineage tracing; metastasis; three dimension; tumor.