Novel Mutations in Cholangiocarcinoma with Low Frequencies Revealed by Whole Mitochondrial Genome Sequencing

Abstract

<b>Background:</b> Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. Thisstudy explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals.Materials and <br/><b>Methods</b>: The whole mitochondrial genome sequences of 25 CCA patient tissues were determinedand compared to those of white blood cells from the corresponding individuals and 12 healthy controls. Themitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge ReferenceSequence. <br/><b>Results</b>: A total of 161 mutations were identified in CCA tissues and the corresponding white bloodcells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequentlyobserved in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrencefrequencies were observed in both groups. <br/><b>Conclusions</b>: While the correspondence between the cancer andmitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in alarger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.