title: Pilocytic astrocytoma: a disease with evolving molecular heterogeneity.
abstract: Pilocytic astrocytoma, the most common pediatric brain tumor, is a clinically and molecularly heterogeneous disease that occurs most often in the cerebellum and hypothalamic and chiasmatic regions. Classically, pilocytic astrocytomas are driven by the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Recently described genetic aberrations involving this pathway are critical for tumorigenesis. Tandem duplication of 7q34 encodes BRAF and produces several KIAA1549-BRAF novel oncogenic fusions. Activating point mutations of BRAF, such as BRAF (V600E), also lead to pilocytic astrocytoma. Loss of the NF1 gene allows hyperactivation of the oncogene KRAS. In this review, we discuss the current understanding of the novel molecular aberrations described in pilocytic astrocytomas and their clinical relevance for prognosis and treatment. The prognostic indications of these aberrations are discussed with regard to tumor location, tumor pathology, and patient age. A better understanding of the evolving molecular heterogeneity of pilocytic astrocytomas offers hope for developing molecularly targeted therapeutic armamentariums.
authors: St. Jude Children's Research Hospital, Memphis, TN 38105, USA. sila.sadighi@stjude.org
authors: Zsila
authors: Z
authors: Sadighi
authors: John
authors: J
authors: Slopis
mesh_terms: D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002528:Cerebellar Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D002648:Child; D002869:Chromosome Aberrations; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D016514:Genes, Neurofibromatosis 1; D018740:Genetic Heterogeneity; D006801:Humans; D007029:Hypothalamic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D058990:Molecular Targeted Therapy; D009897:Optic Chiasm; D019574:Optic Nerve Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D017354:Point Mutation / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015533:Transcriptional Activation / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins