Molecular diagnostics of brain tumors.

摘要: Knowledge about the molecular aberrations driving development and progression of primary central nervous system tumors is steadily increasing, including recent discoveries novel genetic in both pediatric adult brain tumors, such as frequent mutations isocitrate dehydrogenase 1 (IDH1) gene diffuse gliomas or aberrant activation BRAF signaling pilocytic astrocytomas. Importantly, evidence accumulating that certain changes are closely associated with therapy response and/or patient survival, thus making them attractive targets for diagnostic testing aiming to improve treatment stratification prognostic assessment individual patient. Prominent examples markers have elicited substantial clinical interest association MGMT promoter methylation sensitivity alkylating chemotherapy longer survival glioblastoma patients well combined complete loss chromosomal arms 1p 19q a powerful marker (oligodendro)glial tumors. Furthermore, mutation status IDH1, either by immunohistochemistry DNA sequencing, has been identified gliomas, while detection may facilitate diagnosis astrocytomas [1]. Similarly, studies on embryonal (CNS) shown medulloblastomas can be molecularly subdivided into pathogenetically distinct subgroups based mRNA profiles indicative different pathways, sonic hedgehog wingless cascades. several linked medulloblastoma patients, most notably amplification MYC MYCN, mutation/nuclear accumulation bcatenin, copy number chromosome 6, 17. Combined these allows greatly improved risk will likely implemented upcoming trials. Moreover, characteristic alterations less common tumor entities, expression SMARCB1 (INI1/ hSNF5) atypical teratoid/rhabdoid focal micro-RNA cluster at 19q13.42 ependymoblastoma/embryonal abundant neuropil true rosettes, respectively [2]. Traditionally, classification grading histopathological immunohistochemical features under light microscope according criteria defined World Health Organization (WHO) system. This morphological analysis, however, tells only ‘part story’ tumor. There no problem long information generated educated analysis histological slide (which fact ‘systematic artifact’ created fixation, further tissue processing, cutting staining tissue) leads highly reproducible conveys required prognosis therapeutic decision-making. However, WHO typing not always precise, G. Reifenberger (&) Department Neuropathology, Heinrich-Heine-University, Dusseldorf, Germany e-mail: reifenberger@med.uni-duesseldorf.de