title: Loss of NF1 alleles distinguish sporadic from NF1-associated pilocytic astrocytomas.
abstract: Pilocytic astrocytomas classified as WHO grade I typically arise in childhood and upon complete surgical removal carry a favorable prognosis. Children with neurofibromatosis 1 (NF1) have a vastly increased risk for pilocytic astrocytomas, especially for those of the optic nerve. Using 4 intragenic NF1 microsatellite markers, we examined losses of NF1 alleles on the long arm of chromosome 17 in 12 NF1-associated and 25 sporadic pilocytic astrocytomas. The TP53 gene region on the short arm of chromosome 17 was also examined in these tumors using 3 markers. Loss of 1 NF1 allele was detected in 11 of 12 (92%) informative NF1-associated pilocytic astrocytomas. In contrast, only 1 of 24 informative (4%) sporadic pilocytic astrocytomas exhibited allelic loss in the NF1 region. Among the 11 NF1-associated tumors with NF1 loss, 5 had also lost alleles on 17p. The high rate of NF1 allele loss in NF1-associated pilocytic astrocytomas suggests a tumor initiating or promoting action of the NF1 gene in these patients. On the other hand, the much lower rate of NF1-allele loss in sporadic pilocytic astrocytomas argues for only minor importance of NF1 in that patient group. The present data support different mechanisms in the formation of NF1-associated and sporadic pilocytic astrocytomas.
authors.affiliation: Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Kluwe
authors.forename: C
authors.initials: C
authors.lastname: Hagel
authors.forename: M
authors.initials: M
authors.lastname: Tatagiba
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Stavrou
authors.forename: H
authors.initials: H
authors.lastname: Ostertag
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
authors.forename: V F
authors.initials: VF
authors.lastname: Mautner
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D002531:Cerebellum; D002886:Chromosomes, Human, Pair 17; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009419:Nerve Tissue Proteins / Q000235:genetics*; D025542:Neurofibromin 1; D009900:Optic Nerve; D013116:Spinal Cord; D013702:Temporal Lobe
chemical_list: D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1