LOW-LEVEL HETEROPLASMY IN HUMAN MITOCHONDRIAL GENOMES OF A CANCER-DERIVED CELL LINE PAIR

In a paired breast cancer and normal cell line, we investigated the link between low-level heteroplasmy, mitogenome mutations, and transcriptome expression. We identified 23 heteroplasmic sites in the two cell lines, where two of the heteroplasmic variants in the normal cells were found as homoplasmic mutations in the cancer cells. We propose that these two sites have become fixed in the cancer cells by selection of low-level heteroplasmic variants already present in the normal cells. By RNA-Seq analysis of the mitochondrial transcriptome we identified upregulated L-strand specific transcripts in the cancer cells. By combination with SNP analysis, we found two homoplasmic mutations in the cancer cell mitochondrial control region that apparently interfere with replication-transcription switching, and represent a plausible explanation for the upregulation of L-strand transcription.