Molecular diagnostics of brain tumors

Excerpt

Knowledge about the molecular aberrations driving the development and progression of primary central nervous system tumors is steadily increasing, including recent discoveries of novel genetic aberrations in both pediatric and adult brain tumors, such as the frequent mutations in the isocitrate dehydrogenase 1 (IDH1) gene in diffuse gliomas or the aberrant activation of BRAF signaling in pilocytic astrocytomas. Importantly, evidence is accumulating that certain molecular changes are closely associated with therapy response and/or patient survival, thus making them attractive targets for molecular diagnostic testing aiming to improve treatment stratification and prognostic assessment of the individual patient. Prominent examples of molecular markers that have elicited substantial clinical interest are the association of MGMT promoter methylation with sensitivity to alkylating chemotherapy and longer survival in glioblastoma patients as well as the combined complete loss of chromosomal arms 1p and 19q as a powerful prognostic marker in patients with (oligodendro)glial tumors. Furthermore, assessment of the mutation status of IDH1, either by immunohistochemistry or by DNA sequencing, has been identified as a powerful diagnostic and prognostic marker in diffuse gliomas, while the detection of BRAF aberrations may facilitate the diagnosis of pilocytic astrocytomas [1]. …