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de Vries, Maurits; Bruijn, Inge Briaire-de; Cleton-Jansen, Anne-Marie; Malessy, Martijn J. A.; van der Mey, Andel G. L.; Hogendoorn, Pancras C. W.
Virchows Archiv : an international journal of pathology, 02/2013, Letnik: 462, Številka: 2Journal Article
Sporadic vestibular schwannomas are benign tumors originating from the Schwann cells of the vestibular portion of the eigth cranial nerve. An important clinical hallmark of these tumors is their variable growth rate. Investigating vestibular schwannoma biology can help to clarify this variable growth rate and may offer targets for therapeutic treatment. A recent mutation analysis on sporadic non-head and neck schwannomas detected BRAF mutations in around 20 % of tumors. BRAF is part of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. MAPK/ERK activation is associated with an uncontrolled cell growth. Mutated BRAF can function as a target to inhibit this pathway. Mutations in BRAF and other members of the MAPK/ERK pathway have not been investigated in sporadic vestibular schwannomas before. The goal of this study was to investigate if these mutations are present in vestibular schwannomas and whether these mutations correlate with tumor growth. Tumor specimens of 48 patients surgically treated for a sporadic vestibular schwannoma were analyzed. An allele-specific quantitative real-time PCR assay was performed to detect the 13 most frequent mutations affecting BRAF , EGFR , PIK3CA , and KRAS . Radiologically measured tumor growth was included in the analysis to identify potential relationships between these mutations and tumor progression. No activating hotspot mutations in BRAF , EGFR , PIK3CA , or KRAS were detected. The 13 most frequent mutations affecting BRAF , EGFR , PIK3CA , and KRAS are not involved in sporadic vestibular schwannoma development. These results are in contrast to the recent detection of these BRAF mutations in non-head and neck schwannomas.
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