Significant existence of deleted mitochondrial DNA in cirrhotic liver surrounding hepatic tumor

Yamamoto, Hideo; Tanaka, Masashi; Katayama, Makoto; Obayashi, Toshihiro; Nimura, Yuji; Ozawa, Takayuki

doi:10.1016/0006-291x(92)91819-c

Cited by 50 publications

(17 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No matched nucleotide changes except for a G-A transition at nucleotide 263, a T-C transition at nucleotide 489, C insertion between nucleotides 311 and 312, a A-G transition at nucleotide 10 398, a C-T transition at nucleotide 10 400, and a C-T transition at nucleotide 16 223 were found in the blood samples; suggesting that the mutations suggested in the present study were not polymorphisms within the mitochondrial genome. Large deletions of nucleotides have been described previously in mtDNA from certain types of tumors (Yamamoto et al, 1992). Despite extensive attempts to find deletions in mtDNA using multiple primers for PCR analysis, we could not detect such deletions in the colorectal mucosa from patients with UC.…”

Section: Discussioncontrasting

confidence: 61%

Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis

et al. 2005

View full text Add to dashboard Cite

We recently reported that oxidative stress elicited by chronic inflammation increases the mutation of mitochondrial DNA (mtDNA) and possibly correlates with precancerous status. Since severe oxidative stress is elicited in the colorectal mucosa of individuals with ulcerative colitis (UC), the possible occurrence of an mtDNA mutation in the inflammatory colorectal mucosa and colitic cancer was investigated. Colorectal mucosal specimens were obtained from individuals with UC with and without colitic cancer and from control subjects. The frequency of mtDNA mutations was higher in colorectal mucosal specimens from patients with UC than that from control subjects. The levels of 8-hydroxy-2 0 -deoxyguanosine, a DNA adduct by reactive oxygen species, were significantly higher in UC than in control. Specimens from patients with colitic cancer contained a significantly higher number of mtDNA mutations. The present observations suggest that the injury followed by the regeneration of colorectal mucosal cells associated with chronic inflammation causes accumulation of mtDNA mutations. The increased instability of genes, including those on the mtDNA, is consistent with the high and multicentric incidence of colorectal cancer in individuals with UC. Thus, analysis of mtDNA could provide a new criterion for the therapeutic evaluation, and may be useful for the prediction of risk of carcinogenesis.

show abstract

Section: Discussioncontrasting

confidence: 61%

Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis

et al. 2005

View full text Add to dashboard Cite

show abstract

“…The level of deletion was also found to be increased in cirrhosis of the liver (Yamamoto et al 1992).…”

Section: Introductionmentioning

confidence: 89%

Detection of the age-dependent 4977 bp deletion of mitochondrial DNA

Meißner

Wurmb

Oehmichen

1997

International Journal of Legal Medicine

View full text Add to dashboard Cite

In recent years a number of mitochondrial DNA (mtDNA) deletions have been detected in various tissues from individuals over 20 years of age. It has been postulated that these deletions are associated with natural aging. In order to determine whether a correlation exists between age and the amount of deleted 4977 bp mtDNA, we used two PCR reactions to study total DNA (nuclear and mitochondrial DNA) extracted from skeletal muscle (m. iliopsoas) obtained at autopsy from 93 individuals representing a wide age spectrum (range: 3 months-97 years). The primer pair L15/H15 was used to amplify a 533 bp fragment of intact mtDNA to determine the percentage of total DNA. A second PCR with the primer pair L35/H35 was then employed to amplify a 667 bp fragment of the deleted mtDNA. The amount of template DNA necessary to amplify the specific fragments of deleted mtDNA was found to decrease with age. Whereas no 4977 bp deletion could be detected in subjects under 20 years of age even with 1000 ng of total DNA, in individuals aged 21 to 30 years 1000 ng total DNA were sufficient. Only 1 ng total DNA was needed in all individuals over 70. Our results show that the 4977 bp deletion can be a useful marker of natural aging in human subjects.

show abstract

“…We have performed many sequencing analyses of nuclear genes from the same ten lines studied here for mtDNA mutations, and estimate that the prevalence of mutations is at least 10-fold higher in the mitochondrial genome than in the nuclear genome of these cells. Previous experiments have demonstrated large deletions in mtDNA, rather than subtle mutations as observed here, in some tumours [21][22][23][24][25] . No deletions were observed in the lines we studied, despite several attempts to find them using multiple primer pairs in PCR-based strategies.…”

mentioning

confidence: 89%

“…The mutations we observed were homoplasmic, whereas the deletions observed in tumour cells or normal cells of aging individuals were generally heteroplasmic, present only in a small proportion of the mitochondrial population [21][22][23][24][25][26] . Our results agree with a previous study 25 in which no somatic mutations in 200 bp of D loop sequence were found.…”

mentioning

confidence: 99%

Somatic mutations of the mitochondrial genome in human colorectal tumours

et al. 1998

View full text Add to dashboard Cite

Alterations of oxidative phosphorylation in tumour cells were originally believed to have a causative role in cancerous growth. More recently, mitochondria have again received attention with regards to neoplasia, largely because of their role in apoptosis and other aspects of tumour biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generation in this organelle, coupled with a low level of DNA repair. However, no detailed analysis of mitochondrial DNA in human tumours has yet been reported. In this study, we analysed the complete mtDNA genome of ten human colorectal cancer cell lines by sequencing and found mutations in seven (70%). The majority of mutations were transitions at purines, consistent with an ROS-related derivation. The mutations were somatic, and those evaluated occurred in the primary tumour from which the cell line was derived. Most of the mutations were homoplasmic, indicating that the mutant genome was dominant at the intracellular and intercellular levels. We showed that mitochondria can rapidly become homogeneous in colorectal cancer cells using cell fusions. These findings provide the first examples of homoplasmic mutations in the mtDNA of tumour cells and have potential implications for the abnormal metabolic and apoptotic processes in cancer.

show abstract

Significant existence of deleted mitochondrial DNA in cirrhotic liver surrounding hepatic tumor

Cited by 50 publications

References 21 publications

Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis

Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis

Detection of the age-dependent 4977 bp deletion of mitochondrial DNA

Somatic mutations of the mitochondrial genome in human colorectal tumours

Contact Info

Product

Resources

About