Impact of Molecular Markers on Personalised-Treatment Concepts in Gliomas
European Association of NeuroOncology Magazine 2014; 4 (3): 109-115
PDF Summary Figures
Keywords: GBM, glioblastoma multiforme, IDH mutation, LGG, LOH 1p/19q, low-grade glioma, MGMT, personalised therapy
Gliomas are rare brain-derived tumours classified according to mainly histopathological criteria by a 4-step grading system of the World Health Organisation (WHO grades I–IV). Differentiating between the underlying tumour cell components (eg, astrocytomas, oligodendrogliomas, ependymomas), grading intends to give clinicians a general estimation about their patients’ prognoses. Increasing knowledge about the molecular genetic profile now leads to a deeper insight into the predictive or prognostic value of several molecular markers with large impact on the treatment of glioma patients.
Hypermethylation of the 6O-methylguanine- DNA methyltransferase (MGMT) promoter has turned out to be an important predictive marker for patients with glioblastoma multiforme (GBM, WHO grade IV) receiving radiochemotherapy with concurrent and adjuvant temozolomide chemotherapy and may be crucial for a treatment decision between (radio-) chemotherapy versus radiation only in older patients. Moreover, mutations of the isocitrate dehydrogenase (IDH) seem to have a strong prognostic impact in malignant gliomas since GBM patients with IDH mutation showed longer median survival compared to patients with anaplastic gliomas (WHO grade III) without IDH mutation. Additionally, genetic co-deletion on chromosomes 1p and 19q (LOH 1p/19q) has been demonstrated to be a favourable prognostic factor for patients with anaplastic gliomas receiving radiation, chemotherapy with alkylating agents, or both.
Hence, histological diagnosis will not be suffi cient to render the best medical treatment to glioma patients in the future. Determination especially of MGMT promoter methylation status, IDH mutation, and LOH1p/19q amongst others will have increasing influence on decision-making in order to meet the demand for more personalised therapy for glioma patients.