Molecular analysis at the NF1 locus in astrocytic brain tumors.

Patients with neurofibromatosis type 1 (NF1) are at increased risk for developing malignant neural crest tumors and juvenile myeloid leukemia. Although the normal allele of the NF1 tumor-suppressor gene is frequently deleted in some of the malignant tumors that arise in patients with NF1, the role of NF1 alterations in the sporadic forms of these cancers is unclear. A series of intragenic sequence polymorphisms was used to investigate lymphocyte and tumor DNA samples from 22 adults with high grade malignant gliomas for loss of heterozygosity (LOH) at NF1. In addition, an assay based on the polymerase chain reaction was used to screen these tumors for point mutations at codon 1423. One recurrent anaplastic astrocytoma showed LOH within NF1 but not with a flanking marker located near the gene. Of 21 informative tumors, none showed point mutations affecting codon 1423 of NF1. These data suggest that LOH at NF1 is uncommon in sporadic high grade astrocytoma, and codon 1423 is not a "hot spot" for activating point mutations in these tumors.