Mutacje mitochondrialnego DNA w rozwoju nowotworów głowy i szyi

Abstract

Data reported until today suggested a pivotal role of nuclear DNA mutations in the process of carcinogenesis. Recently more and more authors claim that disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA have been reported in many cancers of head and neck region. Mitochondrial D-loop has been proven to be mutation hot - spot with majority of mutations in the positions 303 to 315 of poly-C tract. Data show that 37% of patients with premalignant lesions and 62% with carcinoma in situ are positive for mtDNA mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6 were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured in similar number of cases. Neoplastic cells undifferentiation and disease progression is accompanied by multiplication of mtDNA number and increased mtDNA content. mtDNA content corellates with the stage of the disease. mtDNA mutations faciliate cell proliferation and inhibit apoptosis by increasing the production of ractive oxygen species (ROS). Cells harbouring mutated mtDNA have increased proliferation rate, as increased ROS concentration may act as an endogenous growth factor.

Mitochondrial genotype and breast cancer predisposition

“…A number of genetic biomarkers should be developed for routine use. The immediate challenge now is to learn how to use the molecular characteristics of an individual to improve early detection and ultimately to decrease breast cancer morbidity (1,18,34,37).…”

“…It is likely that additional genetic loci contribute to breast cancer susceptibility. In this regard, mitochondrial genetics may be important in carcinogenesis (18,19) and is an important area in oncology research (20)(21)(22). Breast nipple aspirate fluid (NAF) with mtDNA mutations at positions 204, 207 and 16293 has been associated with breast cancer (23) and mtDNA D-loop mutations have been proposed as an independent prognostic marker in breast cancer (24).…”

“…There is an association between somatic mtDNA mutations and cancer development, progression and metastasis (18,21,(30)(31)(32)(33)(34)(35)(36)(37). In addition, recent studies have shown that inherited polymorphisms or mutations of the mitochondrial genome may modulate the risk of developing cancer, including prostate, oral and colorectal cancers (18,(38)(39)(40)(41).…”

“…In addition, recent studies have shown that inherited polymorphisms or mutations of the mitochondrial genome may modulate the risk of developing cancer, including prostate, oral and colorectal cancers (18,(38)(39)(40)(41). Somatic mtDNA mutations have been described in various types of human cancers including bladder, brain, breast, colon, head and neck, lung, ovaries, prostate, thyroid, and breast cancers (20,21,31,33).…”

Association between mitochondrial DNA variations and schizophrenia in the northern Chinese Han population

“…Mitochondria dysfunction can severely affect neuronal activity, including synaptic connection, axon formation, and neuronal plasticity [ 5 ]. Other investigators determined that variations in mtDNA altered the construction and expression levels of relevant proteins [ 6 ]. These variations can yield defects in respiration, enhance glycolysis, and induce overproduction of reactive oxygen species (ROS) [ 7 ].…”