Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1.
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.
Gutmann
D H
DH
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. gutmannd@neuro.wustl.edu
James
C D
CD
Poyhonen
M
M
Louis
D N
DN
Ferner
R
R
Guha
A
A
Hariharan
S
S
Viskochil
D
D
Perry
A
A
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
D025542:Neurofibromin 1