Mitochondrial D-Loop Polymorphism and Microsatellite Instability in Prostate Cancer and Benign Hyperplasia Patients

Abstract

In this study mitochondrial D-Loop variations in Iranian prostate cancer and benign prostatic hyperplasia (BPH) patients were investigated. Tumour samples and corresponding non-cancerous prostate tissue from 40 prostate cancer patients and 40 age-matched BPH patients were collected. The entire mtD-loop region (16024-576) was amplified using the PCR method and products were gel-purified and subjected to direct nucleotide sequencing. A total of 129 variations were found, the most frequent being 263AgG and 310TgC among both BPH and prostate cancer patients. Variation of 309 CgT was significantly more frequent in prostate cancer patients (P value<0.05). Four novel variations were observed on comparison with the MITOMAP database. Novel variations were np16154delT, np366GgA, np389GgA and 56insT. There was no correspondence between the different variations and the age of subjects. Considering that D-loop variations were frequent in both BPH and prostate cancer patients in our study, the fact that both groups had high average age can be a possible contributing factor. D-loop polymorphisms and microsatellite instability can influence cell physiology and result in a benign or malignant phenotype. Significantly higher frequency of 309 CgT variation in cancer patients is a notable finding and must be a focus of attention in future studies.

The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer

“…However, the C16069T polymorphism has been reported in prostate cancer [25], pancreatic cancer [26], endometrial cancer [27], breast cancer [28,29], repeated pregnancy loss [30] and age-related macular degeneration [31]. This result supports our hypothesis, which shows the potential of specific mitochondrial 16069 polymorphism involvement in carcinogenesis.…”

The Mitochondrial DNA Control Region Might Have Useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors

“…For this reason, in the literature, it is assumed that a mutation in the D-loop can modulate the mtDNA copy number, subsequent OXPHOS dysfunction, and increased ROS [11]. The CR of the mtDNA is a hotspot for both germline and somatic mtDNA alterations in various types of tumors such as head and neck, colorectal, lung, bladder, uterine cervix and breast cancers as well as melanoma [12][13][14]. Moreover, several studies have reported that mtDNA polymorphisms and mitochondrial haplogroups have either a predisposing or protective role in various cancer types [15].…”

The Mitochondrial DNA Control Region might have useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors

“…The CR region of the mtDNA is the hotspot for both germline and somatic mtDNA alterations. In addition, the most frequent DNA alterations in the mitochondrial genome were reported in the hypervariable segment-1 (HSV1, np 16204-16383) and -2 (np 57-373) of the CR, which were mostly located in the D-loop, at various types of tumors such as head and neck, colorectal, lung, bladder, melanoma, uterine cervix and breast cancer (Ashtiani et al, 2012;Cai et al, 2011;Zhang et al, 2015). Further associations were also established between single nucleotide polymorphisms (SNPs) of the CR and various complex diseases such as; metabolic syndrome, type II diabetes mellitus (DM), neurodegenerative diseases and aging in literature (Ghezzi et al, 2005;Guney et al, 2014;Mueller et al, 2011;Tipirisetti et al, 2014;Zhang et al, 2015).…”