Mitochondrial DNA mutations in human tumor cells

Li, Hui; Hong, Ze-Hui

doi:10.3892/ol.2012.874

Cited by 10 publications

(9 citation statements)

References 42 publications

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“…Further, we conducted statistical analysis on the status of the base pairs for the point somatic mutations, except for 52 somatic mutations lacking information regarding the status of the base pairs. We found that the most frequent (52.48%) of the somatic point mutations were homoplasmic, and 45.76% were heterogenetic, which agrees with the results of a previous study (Li and Hong, 2012;Yu, 2012) and the fact that cell fission with somatic mtDNA mutations increase the number of and fix mutant types in tumor tissue (Polyak et al, 1998;Penta et al, 2001). We also found that most point mutations were transitions between pyridine and purines (12.70%; 71/559); this mutation pattern was similar to that of oxidative decay on DNA caused by ROS in normal tissues, and may explain the elevated levels of ROS during the tumor development (Beckman and Ames, 1997).…”

Section: Resultssupporting

confidence: 81%

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Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome

Chen

Shi

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The mitochondrion is a crucial intracellular organelle responsible for regulating cellular energy metabolism, producing free radicals, initiating and executing the apoptotic pathways. Previous studies have shown that somatic mutations in mitochondrial DNA are associated with various tumors, which may be involved during carcinogenesis and tumor progression. To examine the mutation pattern in cancer, 625 reported somatic mutations in the mitochondrial DNA genome were analyzed. We found that, except for deletions and insertions, most somatic mutations were point mutations, accounting for 89.44% of somatic mutations. Transition was the predominant form of X.Z. Chen et al. 4332©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 4331-4337 (2015) somatic mutation in the entire mitochondrial DNA genome, accounting for 87.12% of point mutations, most of which were homoplastic. Frequency statistics analysis of point mutations indicated that, except for 3 tRNA genes, the mutations were distributed on all resting genes and in the D-loop region, with the latter showing the highest frequency of somatic mutation (19.34%), followed by the tRNA leucine 2 gene and non-coding regions between base pairs 5892 and 5903, while 13 coding-region genes and 2 rRNA genes showed a relatively lower frequency of somatic point mutations. Nonsynonymous mutations and terminal amino acid changes were the primary point somatic mutations detected from 13 coding-region genes, which may cause mitochondrial dysfunction in cancer cells. We found that the somatic mutations may affect the mitochondrial DNA genome; the non-coding region should be examined to identify somatic mutations as potential diagnostic biomarkers for early detection of cancer.

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Section: Resultssupporting

confidence: 81%

“…Somatic mutations were classified as point mutations, deletions, or insertions according to previous studies (Li and Hong, 2012;Yu, 2012). The spectrum of somatic mtDNA mutations in common primary human malignancies and other diseases were calculated.…”

Section: Methodsmentioning

confidence: 99%

Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome

Chen

Shi

et al. 2015

Genet. Mol. Res.

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“…Clearly, a defective respiratory chain results in mitochondrial ROS release, which not only contributes to triggering of a NF-jB/AP-1-mediated response but may also lead to a vicious cycle of oxidationinduced mutations of mtDNA/nDNA and chromosomal instability (Li and Hong 2012). To this end, it is striking that a high statistical association was observed between mitochondrial disorders and lymphoid malignancies (Mende et al 2007) and that leukemias are among cancers in which mitochondrial dysfunctions and mtDNA mutations are most common (e.g., He et al 2003;Linnartz et al 2004;Piccoli et al 2008;Schildgen et al 2011;Yao et al 2007).…”

Section: Cancermentioning

confidence: 99%

Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications

Kamiński

Röth

Krammer

et al. 2013

Arch. Immunol. Ther. Exp.

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“…Apoptosis reduction promote the tumorigenesis and tumor progress [29]. TUNEL method was used to analyze the effect of HGF and PKG II on apoptosis of AGS and HGC-27 cells.…”

Section: Resultsmentioning

confidence: 99%

PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells

Yao²,

Zhu

et al. 2016

Oncotarget

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Previous studies showed that type II cGMP-dependent protein kinase G (PKG II) could inhibit the activation of epidermal growth factor receptor (EGFR). Both c-Met and EGFR belong to family of receptor tyrosine kinases (RTKs) and have high molecular analogy. However, the effect of PKG II on c-Met activation is unclear. This study was designed to investigate the inhibitory effect of PKG II on the activation of c-Met and consequent biological activities. The results from CCK8 assay, Transwell assay and TUNEL assay showed that HGF enhanced cell proliferation and migration, and decreased cell apoptosis. Activated PKG II reversed the above changes caused by HGF. Immunoprecipitation and Western blotting results showed that PKG II could bind with c-Met and phosphorylate its Ser985, and thereby inhibited HGF-induced activation of c-Met and MAPK/ERK and PI3K/Akt/mTOR mediated signal transduction. When Ser985 of c-Met was mutated to Alanine for preventing phosphorylation of this site, the blocking effect of PKG II on c-Met activation was annulled. When Ser985 of c-Met was mutated to Aspartic acid for mimicking phosphorylation of this site, HGF-induced activation of c-Met was prevented. In conclusion, the results indicated that PKG II could block c-Met activation via phosphorylating Ser985 of this RTK.

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Mitochondrial DNA mutations in human tumor cells

Cited by 10 publications

References 42 publications

Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome

Deciphering the spectrum of somatic mutations in the entire mitochondrial DNA genome

Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications

PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells

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