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Molecular characterization of disseminated pilocytic astrocytomas
Author(s) -
Gessi M.,
Engels A. C.,
Lambert S.,
Rothämel T.,
Hornstein S.,
Collins V. P.,
Denkhaus D.,
Gnekow A.,
Pietsch T.
Publication year - 2016
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12256
Subject(s) - pilocytic astrocytoma , neuroblastoma ras viral oncogene homolog , hras , pathology , kras , astrocytoma , fluorescence in situ hybridization , biology , cancer research , glioma , medicine , gene , mutation , genetics , chromosome
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.