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  4. Tracing of Human Tumor Cell Lineages by Mitochondrial Mutations
 
research article

Tracing of Human Tumor Cell Lineages by Mitochondrial Mutations

Refinetti, Paulo  
•
Morgenthaler, Stephan  
•
Thilly, William G.
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December 3, 2020
Frontiers In Oncology

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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articles-10-3389-fonc-2020-523860.pdf

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