Anna Ścińska

Mutacje mitochondrialnego DNA w rozwoju nowotworów głowy i szyi

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.Summary 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.

Markery metaboliczne nowotworów głowy i szyi – aplikacje kliniczne i podłoże biochemiczne☆

Summary The problem of diagnosis in the field of head and neck region is still valid. Specific diagnosis and precise estimation of the tumors size with the use of CT and MRI imaging is generally unsatisfactory. The Positron Emission Tomography (PET) supports this process with additional information about the tumors metabolism. Numerous publications show that PET-CT has a great influence on the evaluation of the size of the tumor, presence of lymph node metastases, choice of treatment and the prognosis of the recurrence. Cancer cells represent a specific metabolic state. These cells intake large quantities of glucose and utilize it in the process of glycolysis. The oxidative phosphorylation is not efficient in the transformed cells and defects in mitochondrial functions are at the heart of malignant cell transformation. Disruption of the oxidative phosphorylation chain has been described in the neoplasms. As a consequence, in cancer the glycolysis is active even in the normoxic environment. This metabolic shift in cell transformation has been described in early XX century and so called Warburgs hypothesis profoundly influenced the present perception of cancer metabolism, positioning what is termed aerobic glycolysis in the mainstream of clinical oncology. Today we know that neoplastic cells differ at the proteomic level. A subset of different proteins such as hexokinase II or HIF are upregulated. These abnormalities might be used as the neoplastic markers.The problem of diagnosis in the field of head and neck region is still valid. Specific diagnosis and precise estimation of the tumors size with the use of CT and MRI imaging is generally unsatisfactory. The Positron Emission Tomography (PET) supports this process with additional information about the tumors metabolism. Numerous publications show that PET-CT has a great influence on the evaluation of the size of the tumor, presence of lymph node metastases, choice of treatment and the prognosis of the recurrence. Cancer cells represent a specific metabolic state. These cells intake large quantities of glucose and utilize it in the process of glycolysis. The oxidative phosphorylation is not efficient in the transformed cells and defects in mitochondrial functions are at the heart of malignant cell transformation. Disruption of the oxidative phosphorylation chain has been described in the neoplasms. As a consequence, in cancer the glycolysis is active even in the normoxic environment. This metabolic shift in cell transformation has been described in early XX century and so called Warburgs hypothesis profoundly influenced the present perception of cancer metabolism, positioning what is termed aerobic glycolysis in the mainstream of clinical oncology. Today we know that neoplastic cells differ at the proteomic level. A subset of different proteins such as hexokinase II or HIF are upregulated. These abnormalities might be used as the neoplastic markers.