High Rate of Mutation in Mitochondrial DNA Displacement Loop Region in Human Colorectal Cancer

Akouchekian, Mansoureh; Houshmand, Massoud; Hemati, Simin; Ansaripour, Mohammad; Shafa, Mehdi

doi:10.1007/dcr.0b013e31819acb99

Cited by 38 publications

(32 citation statements)

References 18 publications

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“…This was significantly decreased to 2 and 10 in the normal group (Table 2). Previous investigations have shown a high rate of mutations in D-loop region in some cancers such as colorectal or gastric cancers [21,22]; some of these mutations are associated with special community haplogroups. Therefore, it could be concluded that D-loop mutations disrupt apoptosis in two direction; they can either cause an uncontrolled cell proliferation (cancers) and arrest or a decreased cell proliferation (degenerative disorders or growth arrest in fetus).…”

Section: Discussionmentioning

confidence: 98%

“…D-loop has been demonstrated as a mutation 'hot spot' in some disorders such as cancers. The rate of mutations in D-loop is much higher than in other parts of mtDNA, and such alterations can affect the transcription or translation of mtDNA [21].…”

Section: Discussionmentioning

confidence: 99%

“…The RPL women did not have any deletions in mitochondrial genome. Deletions have been found in mtDNA in various cancers [21,22] and mitochondrial myopathies [23]. Such deletions can interfere with cell proliferation and could be possibly observed in somatic cell disorders.…”

Section: Discussionmentioning

confidence: 99%

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No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

Seyedhassani

Houshmand

Kalantar

et al. 2010

J Assist Reprod Genet

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Purpose Repeated pregnancy loss (RPL) occurs in 1 out of 300 couples, and the cause of about 50% of them remains idiopathic. Mitochondria have an important role in human development through ATP production and their involvement in apoptosis. Methods 96 RPL and 96 control females were used to investigate the frequency of deletions and point mutations in the displacement loop (D-loop) on mitochondria. Multiplex PCR and DNA sequencing methods were used to detect possible variations in the mitochondrial DNA (mtDNA).Results No deletions but a high frequency of point mutations were found in RPL females; among 129 variations observed in RPL, 22 mutations were significant (P<0.05) and the insertion of C in nucleotide 114 was novel. Conclusion High rate of mutations in D-loop of mtDNA was observed in maternal blood, a fact that may have a direct or indirect role in inducing RPL. The results can be used in the assessment of RPL and designing possible treatments for improving assisted reproduction.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

Seyedhassani

Houshmand

Kalantar

et al. 2010

J Assist Reprod Genet

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“…Damage to and somatic mutations of mtDNA may lead to impairment of the OXPHOS system and increased ROS production, which subsequently enhances the rate of DNA mutations (8). Numerous researchers have reported that mtDNA mutations or polymorphisms, particularly in the D-loop region, were detected in different types of cancer, including human colorectal (9), ovarian (10) and thyroid (11) cancer, in addition to HCC (12). Furthermore, the association between mtDNA polymorphisms or mutations and the prognoses of cancer has also been investigated, but the results have been ambiguous.…”

Section: Introductionmentioning

confidence: 99%

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Wan

Peng

et al. 2016

Oncology Letters

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Abstract. The association between mitochondrial DNA (mtDNA) polymorphisms or mutations and the prognoses of cancer have been investigated previously, but the results have been ambiguous. In the present study, the associations between sequence variations in the mtDNA D-loop region and the outcomes of patients with hepatocellular carcinoma (HCC) were analysed. A total of 140 patients with HCC (123 males and 17 females), who were hospitalised to undergo radical resection, were studied. Polymerase chain reaction and direct sequencing were performed to detect the sequence variations in the mtDNA D-loop region. Multivariate and univariate analyses were conducted to determine important factors in the prognosis of HCC. A total of 150 point sequence variations were observed in the 140 cases (13 point mutations, 8 insertions, 20 deletions and 116 polymorphisms). The variation rate was 13.4% (150/1, 122). mtDNA nucleotide 150 (C/T) was an independent factor in the logistic regression for early/late recurrence of HCC. Patients with 150T appeared to have later recurrences. In a Cox proportional hazards regression model, hepatitis B virus DNA, Child-Pugh class, differentiation degree, tumour-node-metastasis (TNM) stage, nucleotide 16263 (T/C) and nucleotide 315 (N/insertion C) were independent factors for tumour-free survival time. Patients with the 16263T allele had a greater tumour-free survival time than patients with the 16263C allele. Similarly, patients with 315 insertion C had a superior tumour-free survival time when compared with patients with 315 N (normal). In the Cox proportional hazards regression model, recurrence type (early/late), Child-Pugh class, TNM stage and adjuvant treatment after tumour recurrence (none or one/more than one treatment) were independent factors for overall survival. None of the mtDNA variations served as independent factors. Patients with late recurrence, Child-Pugh class A, and low TNM stages and/or those who received more than one adjuvant treatment following tumour recurrence had favourable outcomes. mtDNA D-loop polymorphisms were associated with early recurrence and tumour-free survival time, but not with overall survival. mtDNA D-loop mutations in HCC were infrequent and lacked prognostic utility. The detection of mtDNA D-loop polymorphisms may assist in identifying risk factors for HCC prognosis, particularly for the short-term outcome, thereby aiding the construction of an appropriate therapeutic strategy.

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“…[10] D-loop mutations have been detected in a wide variety of cancers. [11][12][13][14][15] In particular, the D310 mononucleotide repeat within the D-loop is a hotspot for somatic mutations in colorectal, [16] gastric, [17] lung, [18] and thyroid tumors. [19] Mutations in the D514 region have been associated with thyroid tumors.…”

Section: Introductionmentioning

confidence: 99%

Absence of correlation between serum CRP levels and mitochondrial D-loop DNA mutations in gastro-oesophageal adenocarcinoma

et al. 2014

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High Rate of Mutation in Mitochondrial DNA Displacement Loop Region in Human Colorectal Cancer

Abstract: Mutations in mtDNA D-loop region probably do not cause colorectal cancer but are more likely to be epiphenomena; patients with the high mtDNA variants are at a higher risk of colorectal cancer.

Cited by 38 publications

References 18 publications

No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

No mitochondrial DNA deletions but more D-loop point mutations in repeated pregnancy loss

Associations between sequence variations in the mitochondrial DNA D-loop region and outcome of hepatocellular carcinoma

Absence of correlation between serum CRP levels and mitochondrial D-loop DNA mutations in gastro-oesophageal adenocarcinoma

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