Genetic and Epigenetic Factors Affecting Development and Prognosis of Brain Gliomas - a Review of Current Knowledge
Abstract
Gliomas represent a heterogenous group of primary brain tumors that can significantly vary in prognosis and treatment. The WHO Brain Tumors classification is based on morphological criteria that seem inadequate as they do not reflect new molecular markers.
These new markers affect prognosis, overall survival and treatment more than histological diagnosis. IDH1/2 mutation and 1p/19q codeletion are the most important molecular markers predicting patient prognosis in lower grade gliomas and secondary glioblastomas.
IDH1/2 mutation is a marker of better prognosis than wild type IDH. Similarly, ATRX plays an important role in anaplastic astrocytomas and loss of ATRX expression positively affects treatment response in these tumors.
Clinical studies suggest that 1p/19q codeletion is the most relevant prognostic marker in oligodendroglial tumors, probably because of tumor chemosensitivity. Besides 1p/19q codeletion, TERT promoter mutation is another important factor in overall survival.
Patients with gliomas carrying combined IDH1/2 mutation and 1p/19q codeletion have the best prognosis compared to those with wild type IDH. Glioblastomas are highly malignant glial tumors.
Despite the progress in understanding of tumor formation and development, they are still difficult to treat. Nevertheless, MGMT promoter methylation in GBM is the most important predictor of good treatment response.
A specific EGFRvIII mutation is another potential treatment target. Recently, single nucleotide polymorphisms (SNP) were found as another, in this case inherited, factor that can have an impact on a patient's prognosis and treatment response.
In particular, rs55705857 in anaplastic oligodendroglioma G allele carriers have much better prognosis in comparison to those who carry A allele. These new findings confirm that the prognosis is affected by multiple factors, including inherited predisposition.