Loss of NF1 alleles distinguish sporadic from NF1-associated pilocytic astrocytomas

Pilocytic astrocytomas classified as WHO grade I typically arise in childho od 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 N F1 microsatellite markers, we examined losses of NF1 alleles. on the long a rm of chromosome 17 in 12 NF1-associated and 25 sporadic pilocytic astrocyt omas. The TP53 gene region on the short arm of chromosome 17 was also exami ned in these tumors using 3 markers. Loss of 1 NF1 allele was detected in 1 1 of 12 (92%) informative NF1-associated pilocytic astrocytomas. In contras t, 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 promot ing action of the NF1 gene in these patients. On the other hand, the much l ower rate of NF1-allele loss in sporadic pilocytic astrocytomas argues for only minor importance of NF1 in that patient group. The present data suppor t different mechanisms in the formation of NF1-associated and sporadic pilo cytic astrocytomas.