Journal
MITOCHONDRIAL DNA PART A
Volume 30, Issue 1, Pages 82-91Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/24701394.2018.1461852
Keywords
Cancer cell; heteroplasmy; lncRNA; mitogenome; mitotranscriptome; SOLiD sequencing
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Funding
- UiT - The Arctic University of Norway
- SpareBank1 Nord-Norge Medical Research Foundation
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Low-level mitochondrial heteroplasmy is a common phenomenon in both normal and cancer cells. Here, we investigate the link between low-level heteroplasmy and mitogenome mutations in a human breast cancer matched cell line by high-throughput sequencing. We identified 23 heteroplasmic sites, of which 15 were common between normal cells (Hs578Bst) and cancer cells (Hs578T). Most sites were clustered within the highly conserved Complex IV and ribosomal RNA genes. Two heteroplasmic variants in normal cells were found as fixed mutations in cancer cells. This indicates a positive selection of these variants in cancer cells. RNA-Seq analysis identified upregulated L-strand specific transcripts in cancer cells, which include three mitochondrial long non-coding RNA molecules. We hypothesize that this is due to two cancer cell-specific mutations in the control region.
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