title: Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1.
abstract: BACKGROUND
  Fifteen to 20% of children with neurofibromatosis type 1 (NF1) develop low-grade astrocytomas. Although brain tumors are less common in teenagers and adults with NF1, recent studies have suggested that patients with NF1 are at a significantly increased risk of developing astrocytomas.
  
  
  OBJECTIVE
  S: To investigate the genetic basis for astrocytoma development in patients with NF1 beyond the first decade of life.
  
  
  METHODS
  The authors performed molecular genetic analyses of 10 NF1-associated astrocytomas representing all World Health Organization (WHO) malignancy grades using fluorescence in situ hybridization, loss of heterozygosity, immunohistochemistry, and direct sequencing.
  
  
  RESULTS
  Later-onset NF1-associated astrocytomas, unlike histologically identical sporadic astrocytomas, exhibit NF1 inactivation, supporting a direct association with NF1 rather than a chance occurrence. Furthermore, some of these astrocytomas have homozygous NF1 deletion. In addition, genetic changes observed in high-grade sporadic astrocytomas, including TP53 mutation and CDKN2A/p16 deletion, are also seen in NF1-associated high-grade astrocytomas.
  
  
  CONCLUSIONS
  Neurofibromatosis type 1-associated astrocytomas occurring in patients older than 10 years exhibit genetic changes observed in sporadic high-grade astrocytomas. Patients with neurofibromatosis type 1 and germline NF1 deletions may be at risk for developing late-onset astrocytomas.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. gutmannd@neuro.wustl.edu
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: C D
authors.initials: CD
authors.lastname: James
authors.forename: M
authors.initials: M
authors.lastname: Poyhonen
authors.forename: D N
authors.initials: DN
authors.lastname: Louis
authors.forename: R
authors.initials: R
authors.lastname: Ferner
authors.forename: A
authors.initials: A
authors.lastname: Guha
authors.forename: S
authors.initials: S
authors.lastname: Hariharan
authors.forename: D
authors.initials: D
authors.lastname: Viskochil
authors.forename: A
authors.initials: A
authors.lastname: Perry
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D016514:Genes, Neurofibromatosis 1; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000150:complications*; D025542:Neurofibromin 1 / Q000032:analysis / Q000276:immunology
chemical_list: D025542:Neurofibromin 1