1. Cancer-specific SNPs originate from low-level heteroplasmic variants in human mitochondrial genomes of a matched cell line pair
- Author
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Steinar Johansen, Erik Knutsen, Tor Erik Jørgensen, Maria Perander, Annica Hedberg, and Anne Silje Løvhaugen
- Subjects
0301 basic medicine ,Mitochondrial DNA ,Single-nucleotide polymorphism ,Biology ,Genome ,Polymorphism, Single Nucleotide ,Cell Line ,Electron Transport Complex IV ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Neoplasms ,Genetics ,medicine ,Humans ,Molecular Biology ,RNA ,Cancer ,medicine.disease ,Heteroplasmy ,030104 developmental biology ,Cell culture ,RNA, Ribosomal ,030220 oncology & carcinogenesis ,Cancer cell ,Genome, Mitochondrial - Abstract
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.
- Published
- 2018