Molecular characterization of disseminated pilocytic astrocytomas. (20th July 2015)

• Record Type: Journal Article
• Authors: Gessi, M.; Engels, A. C.; Lambert, S.; Rothämel, T.; von Hornstein, S.; Collins, V. P.; Denkhaus, D.; Gnekow, A.; Pietsch, T.
• Is Part Of: Neuropathology & applied neurobiology. Volume 42:Number 3(2016)
• Page Start: 273
• Page End: 278
• Publication Date: 2015-07-20
• Subjects: BRAF -- disseminated pilocytic astrocytoma -- ERK -- KIAA1549–BRAF fusion -- low grade gliomas -- MAPK pathway; Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/nan.12256
• Languages: English
• ISSNs: 0305-1846

Abstract

Abstract : Aim: Pilocytic astrocytomas represent the most common paediatric tumours of the central nervous system. Dissemination through the ventricular system occurs rarely in patients with pilocytic astrocytomas; however, it is more common in infants with diencephalic tumours, and is associated with a poor outcome. Despite histological similarities with classic pilocytic astrocytomas, it is still unclear whether disseminated pilocytic astrocytomas may have specific molecular features. Methods: Seventeen disseminated pilocytic astrocytomas were investigated using the molecular inversion probe array and screened for the presence of gene fusions ( KIAA1549‐BRAF ) and mutations ( BRAF, RAS and FGFR1 ). Results: Along with evidence of a constitutive MAPK activation in all cases, the molecular inversion probe array, fluorescence in situ hybridization analysis and mutational study revealed KIAA1549‐BRAF fusions in 66% and BRAF V600E mutations in 5% of cases. No KRAS, HRAS, NRAS or FGFR1 mutations were found. Conclusions: disseminated pilocytic astrocytomas showed genetic features similar to classic pilocytic astrocytoma, including a similar incidence of KIAA1549–BRAF fusions, BRAF mutations and a stable genetic profile. Given common activation of the MAPK pathway, the use of specific inhibitors can be hypothesized for the treatment of disseminated pilocytic astrocytomas, along with standard chemo‐ and/or radiotherapy. Abstract : Disseminated pilocytic astrocytomas in infants share genetic features with classical pilocytic astroctomas suggesting that MAPK inhibitors may have a therapeutic role in both tumour types.