Cancer-specific SNPs originate from low-level heteroplasmic variants in human mitochondrial genomes of a matched cell line pair
| Autor: | Steinar Johansen, Erik Knutsen, Tor Erik Jørgensen, Maria Perander, Annica Hedberg, Anne Silje Løvhaugen |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis. 30(1) |
| ISSN: | 2470-1408 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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