MOLECULAR ANALYSIS AT THE NF1 LOCUS IN ASTROCYTIC BRAIN-TUMORS

Background. Patients with neurofibromatosis type 1 (NF1) are at increa sed risk for developing malignant neural crest tumors and juvenile mye loid 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 form s of these cancers is unclear. Methods. A series of intragenic sequenc e polymorphisms was used to investigate lymphocyte and tumor DNA sampl es from 22 adults with high grade malignant gliomas for loss of hetero zygosity (LOH) al NF1. In addition, an assay based on the polymerase c hain reaction was used to screen these tumors for point mutations at c odon 1423. Results. One recurrent anaplastic astrocytoma showed LOH wi thin NF but not with a flanking marker located near the gene. Of 21 in formative tumors, none showed point mutations affecting codon 1423 of NF1. Conclusion, These data suggest that LOH at NF1 is uncommon in spo radic high grade astrocytoma, and codon 1423 is not a ''hot spot'' for activating point mutations in these tumors.