Heteroplasmic substitutions in the entire mitochondrial genomes of human colon cells detected by ultra-deep 454 sequencing

Skonieczna, Katarzyna; Malyarchuk, B. A.; Jawień, Arkadiusz; Marszałek, Andrzej; Banaszkiewicz, Zbigniew; Jarmocik, Paweł; Borcz, Marcelina; Bała, Piotr; Grzybowski, Tomasz

doi:10.1016/j.fsigen.2014.10.021

Cited by 21 publications

(22 citation statements)

References 38 publications

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“…More importantly, the mtDNA mutational spectrum reconstructed by us for 100 normal specimens (analyzed population sample increased by 50 samples compared with our previous report, Skonieczna et al., ) is similar to that observed in healthy individuals from different populations. Indeed, different studies validated to detect the minority variant at the level of about 10%, showed that point heteroplasmy occurs in about 24%–28% of individuals (Li et al., ; Parson et al., ; Ramos et al., ; Park et al., ).…”

Section: Discussionsupporting

confidence: 88%

“…On the contrary, the accuracy of mitogenomic data presented here was confirmed by a posteriori phylogenetic analysis. Thus, by using the validated 454 sequencing technology (Skonieczna et al., ) we were able to reconstruct a reliable spectrum of mtDNA variability not only in the normal cells, but also in the colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Detailed, validated analysis protocol of the raw data was described by Skonieczna et al. (). The mtDNA sequences obtained by the 454 and the dideoxy sequencing technologies were compared with the revised Cambridge Reference Sequence, rCRS (Andrews et al., ) using GS Reference Mapper v.2.5.3 (Roche Diagnostics GmbH) or SeqScape v.2.5 software (Applied Biosystems, Life Technologies), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, we performed a new study on 100 colorectal cancer patients from the Polish population, in which mitogenomes of normal and corresponding cancer tissues were determined using validated next generation sequencing technology (Skonieczna et al., ), with at least 1,000 × coverage. The haplotypes obtained in this study were subjected to phylogenetic scrutiny, which showed no deviation from the human mitochondrial phylogeny.…”

Section: Introductionmentioning

confidence: 99%

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Mitogenomic differences between the normal and tumor cells of colorectal cancer patients

et al. 2018

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So far, a reliable spectrum of mitochondrial DNA mutations in colorectal cancer cells is still unknown, and neither is their significance in carcinogenesis. Indeed, it remains debatable whether mtDNA mutations are "drivers" or "passengers" of colorectal carcinogenesis. Thus, we analyzed 200 mitogenomes from normal and cancer tissues of 100 colorectal cancer patients. Minority variant mutations were detected at the 1% level. We showed that somatic mutations frequently occur in colorectal cancer cells (75%) and are randomly distributed across the mitochondrial genome. Mutational signatures of somatic mitogenome mutations suggest that they might arise through nucleotide deamination due to oxidative stress. The majority of somatic mutations localized within the coding region (in positions not known from the human phylogeny) and was potentially pathogenic to cell metabolism. Further analysis suggested that the relaxation of negative selection in the mitogenomes of colorectal cancer cells may allow accumulation of somatic mutations. Thus, a shift in glucose metabolism from oxidative phosphorylation to glycolysis may create advantageous conditions for accumulation of mtDNA mutations. Considering the fact that the presence of somatic mtDNA mutations was not associated with any clinicopathological features, we suggested that mtDNA somatic mutations are "passengers" rather than the cause of colorectal carcinogenesis.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitogenomic differences between the normal and tumor cells of colorectal cancer patients

et al. 2018

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“…The complete mitochondrial genome sequences were determined with the dideoxy sequencing method in the same samples (colorectal cancer and normal tissues) collected from 50 patients. The sequencing procedure as well as data‐analysis strategy for determine mtDNA heteroplasmy and quality control were described by Skonieczna et al ().…”

Section: Methodsmentioning

confidence: 99%

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

Linkowska

Jawień

Marszałek

et al. 2015

Annals of Human Genetics

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SummaryMitochondrial 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 (ß92%). 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.

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Exploring statistical weight estimates for mitochondrial DNA matches involving heteroplasmy

et al. 2022

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Heteroplasmic substitutions in the entire mitochondrial genomes of human colon cells detected by ultra-deep 454 sequencing

Cited by 21 publications

References 38 publications

Mitogenomic differences between the normal and tumor cells of colorectal cancer patients

Mitogenomic differences between the normal and tumor cells of colorectal cancer patients

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

Exploring statistical weight estimates for mitochondrial DNA matches involving heteroplasmy

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