Avaliação da integridade genômica mitocondrial em gliomas de alto e baixo grau na população paraense

Abstract

Cancer is characterized by fast abnormal cells proliferation which grow beyond their normal limits and may invade adjacent or distant tissue. Cancer CNS represents 2% of all cancers in the world, being slightly higher in men than in women. Mitochondria are responsible for producing most of the cellular ATP by oxidative phosphorylation (OXPHOS), may also act through glycolysis for same purpose, not requiring only oxygen. This option is a particular cancer cell property, also known as the Warburg effect. One hypothesis to explain this metabolic change may be related to mitochondrial DNA (mtDNA) defects caused by OXPHOS where these mutations can lead cancer cells to glycolysis. Eight mtDNA regions (D-LOOP, ND1, ND3, CO I, CO II CO III, ATPase 6 and ATPase 8) were analyzed in patients’ neoplastic tissues with glial cell cancer in Pará population, relating the data with the pathological and clinical characteristics of the patients. Among the changes found, the complex I seem to be decisive for the progression of high-grade tumors, as well as changes indel seem compromising important structures for OXPHOS. Deletions 4977 bp, when combined with other changes in ND1 / ND3 or heteroplasmias suggest poor prognosis, however, seem to have a reduced risk when changes in ND1 and ND3 are simultaneous.