Sept 2012 – MAPK Signaling as a Therapeutic Target in Optic Nerve Gliomas

Gliomas of the optic nerve represent a specific subtype of low grade astrocytomas with unique clinical properties. However, molecular studies in these tumors have been hampered by the lack of sufficient pathologic material, because surgical resection is now rarely performed. Dr. Rodriguez and colleagues studied archived optic nerve gliomas several decades old from the AFIP using tissue microarray sections with fluorescence in situ hybridization (FISH) and immunohistochemistry. Almost all tumors had pilocytic astrocytoma histology, and the subset of pilocytic astrocytomas with informative FISH and clinical data contained BRAF duplications (11 of 14 cases) or had clinical history of neurofibromatosis type 1 (NF1) (n=4), with one NF1 patient containing a concurrent BRAF duplication. pERK immunoreactivity, consistent with MAPK pathway activation, was present in 55/57  (96%) of tumors tested. Molecular alterations typical of diffuse gliomas (PTEN and CDKN2A deletions, IDH (R132H) mutation) were rare to absent.  The study was published in JNEN(http://www.ncbi.nlm.nih.gov/pubmed/22892521). It confirms that optic nerve gliomas represent primarily pilocytic astrocytomas, and demonstrates MAPK pathway activation in almost all cases, supporting targeting this pathway in patients with aggressive tumors.

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