title: Pediatric brain tumors: loss of heterozygosity at 17p and TP53 gene mutations.
abstract: Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) have demonstrated material losses of 17p, the region that contains the TP53 gene, as the most frequent abnormality. Mutations in the TP53 gene are, however, very rare in these tumors. These findings strongly suggest that another, as yet unidentified, gene on 17p may be involved. We performed a search for loss of heterozygosity (LOH) on 17p by microsatellite markers on 26 childhood CNS tumors as well as TP53 gene mutations (exons 5-8) by single-strand conformational polymorphism analysis on 41 pediatric brain tumor samples of distinct histologic types. LOH was detected in 10 cases: 7 PNET, 2 astrocytomas, and 1 glioblastoma multiforme. In 4 of the PNETs the losses were limited to more distal markers. On the other hand, TP53 mutations were detected in 6 of 41 samples studied. Our results not only confirm the low penetrance of the TP53 gene on pediatric CNS tumors, but also provide further evidence of a putative tumor suppressor gene distal to TP53, between markers (D17S938, D17S926) and 17pter, specifically taking part in the development of PNET.
authors.affiliation: Unidad de Genetica, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Orellana
authors.forename: M
authors.initials: M
authors.lastname: Hernandez-Martí
authors.forename: F
authors.initials: F
authors.lastname: Martínez
authors.forename: V
authors.initials: V
authors.lastname: Castel
authors.forename: J M
authors.initials: JM
authors.lastname: Millán
authors.forename: J A
authors.initials: JA
authors.lastname: Alvarez-Garijo
authors.forename: F
authors.initials: F
authors.lastname: Prieto
authors.forename: L
authors.initials: L
authors.lastname: Badía
mesh_terms: D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004806:Ependymoma / Q000235:genetics; D005260:Female; D018303:Ganglioglioma / Q000235:genetics; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D005909:Glioblastoma / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009442:Neurilemmoma / Q000235:genetics; D019683:Penetrance; D018807:Polymorphism, Single-Stranded Conformational