Background Low-grade gliomas (LGG) are the most common brain tumours in children, represented by heterogeneous pathological entities. BRAF gene alterations have been recently identified as responsible of constitutive activation of the mitogen-activated protein kinase pathway (MAPK) and hence involved in the development of LGG in children. There is evidence that the BRAF V600E mutation is more common in supratentorial LGG while the KIAA1549:BRAF fusion in posterior fossa pilocytic astrocytoma (PA). Objective This case series describes the prevalence of BRAF alterations in LGG patients, trying to relate them to outcome. Methods Children aged 0–14 years, with a diagnosis of LGG, referred to a single neuro-oncologic centre, were retrospectively reviewed to analyze clinical and histopathological features related to BRAF alterations. Results A total of 35 patients were included (16 males, median age 85.5 ± 81.3 months). BRAF mutations were searched on 7/35 children (20 %) resulting positive in 5/7 (71 %). Two of them (40 %) showed the KIAA1549:BRAF fusion. They were both pilocytic astrocytomas located in posterior fossa: 1/2 (50 %) was totally resected, showing stable disease (SD) 1 year after surgey; the other was not surgically treatable and showed a progressive disease during chemotherapy. Three out of five (60 %) presented V600E mutation. All of them were supratentorial: 1 pilomyxoid astrocytoma, treated with two partial resections and subse- quent chemotherapy, was in SD 5 years after diagnosis; 1 diffuse pleomorphic xanthoastrocytoma underwent three partial resections and showed SD after 5 years of vemurafenib; 1 glioneuronal tumor was in SD after complete resection and radiotherapy. Conclusion Our data support the evidence that specific mutations of the BRAF pathway are related to site and histological subtype of brain tumors. This sample is too small to help supporting the hypothesis that these alterations have a prognostic impact. Extent of surgery and localization seem to be the most important prognostic factors.

Prevalence and significance of BRAF alterations in a pediatric population with low-grade gliomas

Liguoro, I.;PILOTTO, Chiara
;
TOSOLINI, Raffaello
;
COGO, Paola
2017

Abstract

Background Low-grade gliomas (LGG) are the most common brain tumours in children, represented by heterogeneous pathological entities. BRAF gene alterations have been recently identified as responsible of constitutive activation of the mitogen-activated protein kinase pathway (MAPK) and hence involved in the development of LGG in children. There is evidence that the BRAF V600E mutation is more common in supratentorial LGG while the KIAA1549:BRAF fusion in posterior fossa pilocytic astrocytoma (PA). Objective This case series describes the prevalence of BRAF alterations in LGG patients, trying to relate them to outcome. Methods Children aged 0–14 years, with a diagnosis of LGG, referred to a single neuro-oncologic centre, were retrospectively reviewed to analyze clinical and histopathological features related to BRAF alterations. Results A total of 35 patients were included (16 males, median age 85.5 ± 81.3 months). BRAF mutations were searched on 7/35 children (20 %) resulting positive in 5/7 (71 %). Two of them (40 %) showed the KIAA1549:BRAF fusion. They were both pilocytic astrocytomas located in posterior fossa: 1/2 (50 %) was totally resected, showing stable disease (SD) 1 year after surgey; the other was not surgically treatable and showed a progressive disease during chemotherapy. Three out of five (60 %) presented V600E mutation. All of them were supratentorial: 1 pilomyxoid astrocytoma, treated with two partial resections and subse- quent chemotherapy, was in SD 5 years after diagnosis; 1 diffuse pleomorphic xanthoastrocytoma underwent three partial resections and showed SD after 5 years of vemurafenib; 1 glioneuronal tumor was in SD after complete resection and radiotherapy. Conclusion Our data support the evidence that specific mutations of the BRAF pathway are related to site and histological subtype of brain tumors. This sample is too small to help supporting the hypothesis that these alterations have a prognostic impact. Extent of surgery and localization seem to be the most important prognostic factors.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11390/1120010
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