title: Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1.
abstract: Neurofibromatosis 1 (NF1) is an autosomal dominant disorder that predisposes sufferers to various forms of neoplasia. Among affected individuals, 15%-20% develop astrocytomas, especially pilocytic astrocytomas (PA), which are benign and classified as grade I by the World Health Organization. They are generally well circumscribed, and their progression is slow. NF1-associated PAs (NF1-PAs) occasionally behave as aggressive tumors. To elucidate underlying genetic events in clinically progressive NF1-PAs, we performed molecular genetic analysis on 12 PAs, including 3 NF1-PAs, for pS3, p16, and epidermal growth factor receptor genes, as well as loss of heterozygosity (LOH) on chromosome 1p, 10, 17, and 19q. None of the obvious genetic alterations typically seen in higher grade astrocytomas were found in 9 sporadic PAs. However, in 2 of 3 NF1-PAs, microsatellite analysis showed LOH10, including the PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene locus, despite the diagnosis of pilocytic astrocytoma;one of these also manifested homozygous deletion of the p16 gene. The other NF1-PA harbored only LOH of the NF1 gene locus (17q). Our preliminary results support the hypothesis that some NF1-PAs differ genetically from sporadic PAs.
authors.affiliation: Department of Neurosurgery, Kumamoto University Medical School, Kumamoto, Japan. ktada@fc.kuh.kumamoto-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Tada
authors.forename: Masato
authors.initials: M
authors.lastname: Kochi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kuratsu
authors.forename: Shoji
authors.initials: S
authors.lastname: Shiraishi
authors.forename: Takanori
authors.initials: T
authors.lastname: Kamiryo
authors.forename: Naoki
authors.initials: N
authors.lastname: Shinojima
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Ushio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000150:complications / Q000235:genetics* / Q000473:pathology*