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Tracing of Human Tumor Cell Lineages by Mitochondrial Mutations
Name
fonc-10-523860.pdf
Description
Published version
Size
2.14 MB
Format
Adobe PDF
Checksum (MD5)
9ebd29be697a38964d0fa67909c40bdd
Author(s) • • • •
Refinetti, Paulo
Morgenthaler, Stephan
Thilly, William G
Arstad, Christian
Ekstrøm, Per O
Date Issued
2020
Journal
Frontiers in Oncology
Publisher
Frontiers Media SA
Version
Final published version
Abstract
© Copyright © 2020 Refinetti, Morgenthaler, Thilly, Arstad and Ekstrøm. 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.
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.3389/FONC.2020.523860