CAG repeat polymorphism in the DNA polymerase γ gene in a Polish population: An association with testicular cancer risk [5]

Maria Sklodowska Curie Memorial Cancer Centre, Gleiwitz, Silesian Voivodeship, Poland
Annals of Oncology (Impact Factor: 7.04). 08/2005; 16(7):1211-2. DOI: 10.1093/annonc/mdi205
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Available from: Iwona Skoneczna, Jan 05, 2014
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    • "Although mutations in POLG have been shown to result in decreased OXPHOS, decreased mtDNA content and human mitochondrial diseases, their role in the pathogenesis of cancer is still unclear. Recent studies demonstrated association of the polymorphism of the CAG repeat in the POLG gene with the risk of testicular germ-cell cancer (Nowak et al., 2005; Blomberg Jensen et al., 2008). Azrak et al. (2012) suggested the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, although differences in CAG repeat length observed between cases and controls were not statistically significant (Azrak et al., 2012). "
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    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. © 2015 John Wiley & Sons Ltd/University College London.
    Annals of Human Genetics 04/2015; 79(5). DOI:10.1111/ahg.12111 · 2.21 Impact Factor
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    • "In the Polish population-specific number of CAG repeats from POLG was significantly more frequent in patients with germ cell tumor than in 55 healthy men (26% versus 11%, respectively ; P ϭ 0.035 Fisher exact test). No significant differences in clinicopathologic features or outcomes were observed between carriers and noncarriers of polymorphic variants [147]. "
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    ABSTRACT: Nuclear transfer technology has uses across theoretical and applied applications, but advances are restricted by continued poor success rates and health problems associated with live offspring. Development of reconstructed embryos is dependent upon numerous interlinking factors relating both to the donor cell and the recipient oocyte. For example, abnormalities in gene expression following somatic cell nuclear transfer (SCNT) have been linked with an inability of the oocyte cytoplasm to sufficiently epigenetically reprogram the nucleus. Furthermore, influences on the propagation of mitochondria and mitochondrial DNA (mtDNA) could be of great importance in determining the early developmental potential of NT embryos and contributing to their genetic identity. mtDNA encodes some of the subunits of the electron transfer chain, responsible for cellular ATP production. The remaining subunits and those factors required for mtDNA replication, transcription and translation are encoded by the nucleus, necessitating precise intergenomic communication. Additionally, regulation of mtDNA copy number, via the processes of mtDNA transcription and replication, is essential for normal preimplantation embryo development and differentiation. Unimaternal transmission following natural fertilization usually results in the presence of a single identical population of mtDNA, homoplasmy. Heteroplasmy can result if mixed populations of mtDNA genomes co-exist. Many abnormalities observed in NT embryos, fetuses, and offspring may be caused by deficiencies in OXPHOS, perhaps resulting in part from heteroplasmic mtDNA populations. Additionally, incompatibilities between the somatic nucleus and the cytoplast may be exacerbated by increased genetic divergence between the two genomes. It is important to ensure that the nucleus is capable of sufficiently regulating mtDNA, requiring a level of compatibility between the two genomes, which may be a function of evolutionary distance. We suggest that abnormal expression of factors such as TFAM and POLG in NT embryos will prematurely drive mtDNA replication, hence impacting on early development.
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