Mitochondrial NADH dehydrogenase polymorphisms are associated with breast cancer in Poland

Abstract

Complex I NADH-oxidoreductase-ubiquinone transports reducing equivalents from the reduced form of NADH to ubiquinone (coenzyme Q-CoQ). The purpose of this study was to analyze mutations in MT-ND1, MT-ND2, MT-ND3 and MT-ND6 genes and their effect on the biochemical properties, structure and functioning of proteins in patients with breast tumours. In research materials, in 50 patients, 28 total polymorphisms and five mutations were detected. Most detected polymorphisms (50 %, 14/28) were observed in MT-ND2 gene. Most of them were silent mutations. Five polymorphisms (m.G3916A, m.C4888T, m.A4918G, m.C5363T, m.C10283T) do not exist in the database. A total of five mutations in 13 patients (13/50) were detected, including two not described in the literature: m.C4987G and m.T10173C. It cannot be excluded that, through the mutations and polymorphism impact on the protein structure, they may cause mitochondrial dysfunction and contribute to the appearance of other changes in mtDNA. The results of our study indicate the presence of homological changes in the sequence of mtDNA in both breast cancer and in some mitochondrial diseases. Mutations in the examined genes in breast cancer may affect the cell and cause its dysfunction, as is the case in mitochondrial diseases.

Mitochondrial D-loop mutations can be detected in sporadic malignant tumours in dogs

“…The differences in energy metabolism of tumour and normal cells are the biochemical basis for speculation about the therapeutic strategies, which in the future can be used for selective killing of tumour cells (5). Previous studies concerned mainly mutations in human mtDNA in carcinogenesis (7,11,12,34). Only a few authors have conducted investigations on the relationship between mutations and carcinogenesis process in dogs (3,22,28,29).…”

“…Analysis of mitochondrial DNA (mtDNA) sequences plays an important role in the studies on population genetics and in medicine, including veterinary medicine (7,11,12,(27)(28)(29)32). Results published in the recent years have indicated the prevalence of mitochondrial DNA mutations in tumour cells, which suggests that they may be cancer-causing agents (7,11,12,28,29,32,34).…”

“…Results published in the recent years have indicated the prevalence of mitochondrial DNA mutations in tumour cells, which suggests that they may be cancer-causing agents (7,11,12,28,29,32,34). Up till now, there has been not stated whether the observed changes in mitochondrial DNA result from the development of tumour or are connected with the process of neoplastic transformation (7,11,12,28,29). GrzybowskaSzatkowska and Slaska (12) report the presence of homological changes in the sequence of mtDNA in breast cancer and some mitochondrial diseases, which indicates that mutations in mtDNA in breast cancer may affect the cell and cause its dysfunction, as in the case of mitochondrial diseases.…”

“…The studies on tumour tissues showed a significant number of somatic mutations in mtDNA (3,7,11,12,22,28,29), especially in the D-loop region which controls replication and transcription of mitochondrial DNA. These mutations can lead to disorders in these processes and cell energy functions (7,11,17).…”

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma

“…For example, Bai et al demonstrated the association of a nine-base pair deletion at nucleotide position 8272 (region V) of the mtDNA with postoperative survival rate in RCC [20]. In addition, mutations in NADH dehydrogenase subunit 1 ( ND1 ), a subunit of oxidative phosphorylation complex, were detected in breast and nasopharyngeal carcinomas [21,22]. Furthermore, Yusnita et al [23] identified 11 missense mutations in ND1 from colorectal tumor tissue specimens.…”