The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer

Chen, Tao; He, Jing; Shen, Lijun; Fang, Hezhi; Nie, Hezhongrong; Jin, Tao; Wei, Xiaosong; Xin, Yijuan; Jiang, Yulin; Li, Hongzhi; Chen, Guorong; Lü, Jianxin; Bai, Yidong

doi:10.1186/1471-2350-12-8

Cited by 110 publications

(94 citation statements)

References 42 publications

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“…In contrast to previous observations [15,17], which are consistent with expectations of higher rates of mtDNA deletion at the late stages of the disease, we observed that the mtDNA 3,867-bp deletion was more likely to be present in younger transgenic mice, in accordance with the recent results of Chen et al [22]. However, compared to wild-type mice, transgenic mice in general demonstrated higher percentages of mtDNA copies with deletions, supporting the previous findings in healthy and affected MJD individuals [17].…”

Section: Discussioncontrasting

confidence: 56%

Patterns of Mitochondrial DNA Damage in Blood and Brain Tissues of a Transgenic Mouse Model of Machado-Joseph Disease

et al. 2012

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Background: Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia caused by a CAG tract expansions in the ATXN3 gene. Patterns of mitochondrial damage associated with pathological findings of brain tissues could provide molecular biomarkers of this disorder. Objective: The potential of mitochondrial DNA (mtDNA) damage as a biomarker of MJD progression was investigated using a transgenic mouse model. Methods: DNA was obtained from affected (pontine nuclei) and nonaffected tissues (hippocampus and blood) of transgenic animals of three distinct age groups: 8 weeks, before onset of the phenotype; 16 weeks, at onset, and 24 weeks, at well-established phenotype. Wild-type littermate mice, serving as controls, were analyzed for the same tissues and age groups. mtDNA damage was studied by fluorescence-based quantitative PCR in 84 transgenic and 93 wild-type samples. Results: A clear pattern of decrease in mtDNA copy number with age and accumulation of 3,867-bp deletions at the initial stages (both being more pronounced in transgenic mice) was observed. Pontine nuclei, the affected tissue in transgenic mice, displayed 1.5 times less copies of mtDNA than nonaffected brain tissue hippocampus (odds ratio = 1.21). Pontine nuclei displayed the highest percentage of mtDNA deletions (6.05% more in transgenic mice). Conclusion: These results suggest that mtDNA damage is related to the initiation of the phenotype in transgenic mice; mtDNA 3,867-bp deletions may be a biomarker of the initial stages of the disease.

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Section: Discussioncontrasting

confidence: 56%

Patterns of Mitochondrial DNA Damage in Blood and Brain Tissues of a Transgenic Mouse Model of Machado-Joseph Disease

et al. 2012

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“…On the other hand, Afshan et al hypothesized that CNV of mtDNA depends on damage and can function as a biomarker of mitochondrial dysfunction in a particular tissue (18). Changes in the copy number of mtDNA have been reported in sporadic colorectal carcinogenesis (19)(20)(21); however, there are few reports on investigations of CNV related to colitis cancer development.…”

mentioning

confidence: 98%

Increased Copy Number Variation of mtDNA in an Array-based Digital PCR Assay Predicts Ulcerative Colitis-associated Colorectal Cancer

Tanaka

Kobunai

Yamamoto

et al. 2017

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Abstract. Aim: Mitochondrial dysfunction plays a central role in carcinogenesis in numerous cancer-related diseases.We examined the copy number variation of mitochondrial DNA (mtDNA) Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD), and disease-related long-standing inflammation results in increased risk of colitic cancer. The cumulative risks of invasive adenocarcinoma have been shown to be 0.5%, 4.1%, and 6.1% at 10, 20, and 30 years, respectively (1), and colitic cancer, especially the advanced type, determines patient outcomes. Currently, in order to detect dysplastic lesions early, colonoscopy together with random and target biopsies are considered to be the most effective detection option, especially for longstanding UC; however, the characteristics of colitic cancer, such as flat mucosal lesions and widespread distribution, make early detection difficult (2). Another problem with surveillance colonoscopy is its invasiveness and cost effectiveness; therefore, we thought that another modality for the detection of colitic cancer and identification of predictors of patients at high risk was needed.As clinical indicators, the extent and severity of inflammation and the duration of disease have been observed to increase the cumulative risk of dysplasia or invasive colorectal cancer in IBD (3-6). From a molecular perspective, we studied genetic variance in non-neoplastic mucosa. We observed lower DNA copy numbers and lower expression of RUNX3 in non-neoplastic rectal mucosa in cancer-free UC patients (UC-nonCa) than in patients with colitic cancer (UC-Ca) (7). In another study, we identified 20 genes that showed differences in expressions between UC-Ca and UC-nonCa mucosae, and we introduced a prediction model that achieved a markedly high accuracy rate of 83% and negative predictive value of 100% (8). These studies contributed to a better understanding of the genetics of colitic cancer and methods of prediction.Recently, the genetic alteration of mitochondrial DNA (mtDNA) has attracted attention as a target for various diseases. The mitochondrion is a small organelle in cells that plays an important role in the production of energy 713 *These Authors contributed equally to this study.

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“…Chen et al investigated the common deletion in tumour tissue and paired non-tumour areas from colorectal cancer patients in the Wenzhou area of China. They found that the common deletion was more likely to be present in patients of younger age (≤65 years) and its level decreased as the cancer stage advanced (Chen et al 2011). In the present study we found that 100% of non-malignant colon and rectal tissues carried the deletion, although it was found to be more prevalent in the rectum.…”

Section: Discussionmentioning

confidence: 95%

Effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer

et al. 2011

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Surgical resection at any location in the body leads to stress response with cellular and subcellular change, leading to tissue damage. The intestine is extremely sensitive to surgical stress with consequent postoperative complications. It has been suggested that the increase of reactive oxygen species as subcellular changes plays an important role in this process. This article focuses on the effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer. Mitochondrial DNA copy number, mitochondrial common deletion and nuclear and mitochondrial 8-oxo-2'-deoxyguanosine content were measured. Both the colon and rectal tissue were significantly damaged either at the nuclear or mitochondrial level. In particular, mitochondrial DNA was more damaged in rectum than in colon. The present investigation found an association between surgical stress and nuclear and mitochondrial DNA damage, suggesting that surgery may generate an increase in free radicals, which trigger a cascade of molecular changes, including alterations in DNA.

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The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer

Cited by 110 publications

References 42 publications

Patterns of Mitochondrial DNA Damage in Blood and Brain Tissues of a Transgenic Mouse Model of Machado-Joseph Disease

Patterns of Mitochondrial DNA Damage in Blood and Brain Tissues of a Transgenic Mouse Model of Machado-Joseph Disease

Increased Copy Number Variation of mtDNA in an Array-based Digital PCR Assay Predicts Ulcerative Colitis-associated Colorectal Cancer

Effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer

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