The Importance of Mutational Drivers in GBM.
Glioblastoma (GBM) is the most aggressive primary brain tumor, providing few effective therapeutic options, given the tumor heterogeneity and the accumulation of different genetic abnormalities that cause treatment failure. The many different genetic and epigenetic alterations present in GBM lead to modification of several major signaling pathways resulting in brain tumor growth, progression, and therapeutic resistance. Many functionally important mutations have been discovered, known as neutral passengers. IDH1/2, EZH2, and DNMT3A are the best known epigenetic modifiers in cancer. These mutations are important in determining disease prognosis such that the status of the MGMT gene is a direct target of chemotherapy. For these reasons, newly developed technologies are necessary to determine new candidate targets for targeted-therapy development in GBM. The determination of mutations will aid in this and in the discovery of combinations of targeted and conventional therapies to improve GBM treatment.
Department of Medical Genetics, Faculty of Medicine, Near East University, Nicosia, Turkish Republic of Northern Cyprus 99138.
Rasime
R
Kalkan
D001932:Brain Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics; D044127:Epigenesis, Genetic; D005909:Glioblastoma / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation; D011379:Prognosis
C000717967:DNMT3A protein, human; D007521:Isocitrate Dehydrogenase; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein