Mitochondrial DNA common deletion is not associated with thyroid, breast and colorectal tumors in Turkish patients

Abstract

Recently, efforts have been focused on mitochondrial DNA changes and their relation to human cancers. Among them, a 4977 bp deletion of mitochondrial DNA, named “common deletion”, has been investigated in several types of tumors, with inconsistent results. In this study, we investigated the presence of the common deletion in tissues from 25 breast, 25 colorectal and 50 thyroid tumors and in the adjacent healthy tissues from Turkish patients. Samples from healthy volunteers were also evaluated for comparison. Two PCR-based methods were used for the detection of the common deletion. First, two pairs of primers were used to amplify wild-type and deleted mtDNA. Then, a highly sensitive nested-PCR was performed, to determine low amounts of deleted genomes. By the first method, wild-type mtDNAs were observed in all samples, but a deletion was observed in only six thyroid samples, by using the nested-PCR method. In conclusion, the mitochondrial common deletion was very rare in our study group and did not appear to be not related with cancer.

Deletion of a 4977-bp Fragment in the Mitochondrial Genome Is Associated with Mitochondrial Disease Severity

“…DNA from ρ 0 cells was used as a blank control in PCR reactions to examine mtDNA copy number. The primers used to quantify the proportion of mtDNA copies harboring the 4,977-bp deletion were as follows [ 14 ]: (forward primer, nucleotides 8,445–8,483), (reverse primer, nucleotides 13,632–13,651), and (TaqMan probe [ 19 ], nucleotides 13,462–13,482). Primers for the mitochondrial ND1 gene used to quantify the mtDNA copy number were as follows: (forward primer, nucleotides 3,928–3,950), (reverse primer, nucleotides 3,842–3,864), and (TaqMan probe, nucleotides 3904–3925).…”

“…Previous reports have focused on associations between point mutations and mitochondrial disease pathogenesis, rather than associations involving larger deletions. Moreover, large population-based studies on the role of ΔmtDNA 4977 are rare, and its function in mitochondrial disease pathogenesis remains heavily disputed [ 8 – 14 ]. One of the critical factors determining the mitochondrial phenotype is the copy number ratio of mutant to wild-type (WT) mtDNA.…”

Mitochondrial Common Deletion, a Potential Biomarker for Cancer Occurrence, Is Selected against in Cancer Background: A Meta-Analysis of 38 Studies

“…Of the 38 studies, sample sizes ranged from 7 to 130, in which nine studies focusing on breast cancer [25], [31]–[38], five studies focusing on hepatocellular carcinoma [39]–[43], four focusing on gastric cancer [38], [44]–[46], three focusing on colorectal cancer [25], [38], [47], three focusing on esophageal cancer [48]–[50], three focusing on oral cancer [51]–[53], two focusing on thyroid cancer [25], [54], two focusing on skin cancer [55], [56] and seven studies of other cancers (one endometrial carcinoma [57], one lung cancer [58], one Warthin’s cancer [59], one cervix cancer [60], one acute lymphoblastic leukemia [61], one prostate cancer [62] and one head and neck cancer [38]). Because some controls in two researches [25], [38] were shared by several cancers, it was defined as four studies (breast cancer, colorectal cancer, gastric cancer and head and neck cancer) and three studies (thyroid cancer, breast cancer and colorectal cancer) in the analysis stratified by cancer type but defined as one study in the overall analysis and stratification analysis by ethnicity, sample size, measurement method and DNA source. Overall, 12 studies used EA, 20 used Asians and one used other ethnic groups.…”

“…These were 27 case/adjacent normal studies and 15 case/healthy normal studies included. Additionally, the tissue was the most common source of DNA, although other sources were also applied, such as blood and buccal swab [25], [32], [38], [48], [49]. Buccal swab was termed as tissue in the stratified analysis by DNA source.…”

“…In some cases, the incidence and level of the 4,977 bp deletion were lower in the cancer tissue compared with adjacent non-cancerous tissue from the same patients [24]. In some reports no significant associations were detected [25]. Mitochondrial DNA deletions serve as biomarkers of aging in the skin, but are typically absent in non melanoma skin cancers.…”