Mitochondrial DNA Polymerase Mutations and Their Implications in mtDNA Alterations in Colorectal Cancer

作者：Linkowska Katarzyna^*; Jawien Arkadiusz; Marszalek Andrzej; Malyarchuk Boris A; Tonska Katarzyna; Bartnik Ewa; Skonieczna Katarzyna; Grzybowski Tomasz

来源：Annals of Human Genetics, 2015, 79(5): 320-328.

DOI：10.1111/ahg.12111

• POLG
• mtDNA
• colorectal cancer
• somatic mutations

Mitochondrial DNA was found to be highly mutated in colorectal cancer cells. One of the key molecules involved in the maintenance of the mitochondrial genome is the nuclear-encoded polymerase gamma. The aim of our study was to determine if there is a link between polymorphisms within the polymerase gamma gene (POLG) and somatic mutations within the mitochondrial genome in cancer cells. We investigated POLG sequence variability in 50 colorectal cancer patients whose complete mitochondrial genome sequences were determined. Relative mtDNA copy number was also determined. We identified 251 sequence variants in the POLG gene. Most of them were germline-specific (approximate to 92%). Twenty-one somatic changes in POLG were found in 10 colorectal cancer patients. We have found no association between the occurrence of mtDNA somatic mutations and the somatically occurring variants in POLG. MtDNA content was reduced in patients carrying somatic variants in POLG or germline nucleotide variants located in the region encoding the POLG polymerase domain, but the difference did not reach statistical significance. Our findings suggest that somatic mtDNA mutations occurring in colorectal cancer are not a consequence of somatic mutations in POLG. Nevertheless, POLG nucleotide variants may lead to a decrease in mtDNA content, and consequently result in mitochondrial dysfunction.

• 出版日期2015-9