title: Mitochondrial DNA Polymerase γ Mutations and Their Implications in mtDNA Alterations in Colorectal Cancer.
abstract: 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 (∼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.
authors: Department of Molecular and Forensic Genetics, Institute of Forensic Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors: Katarzyna
authors: K
authors: Linkowska
authors: Chair of Vascular Surgery and Angiology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors: Arkadiusz
authors: A
authors: Jawień
authors: Chair & Department of Clinical Pathomorphology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors: Andrzej
authors: A
authors: Marszałek
authors: Institute of Biological Problems of the North, Far-East Branch of the Russian Academy of Sciences, Magadan, Russia.
authors: Boris A
authors: BA
authors: Malyarchuk
authors: Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
authors: Katarzyna
authors: K
authors: Tońska
authors: Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Warsaw, Poland.|Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors: Ewa
authors: E
authors: Bartnik
authors: Department of Molecular and Forensic Genetics, Institute of Forensic Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors: Katarzyna
authors: K
authors: Skonieczna
authors: Department of Molecular and Forensic Genetics, Institute of Forensic Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors: Tomasz
authors: T
authors: Grzybowski
keywords: POLG; colorectal cancer; mtDNA; somatic mutations