P53 MUTATION AS THE 2ND EVENT IN JUVENILE CHRONIC MYELOGENOUS LEUKEMIA IN A PATIENT WITH NEUROFIBROMATOSIS TYPE-1

BACKGROUND. Young patients with neurofibromatosis type 1 (NF1) are at increased risk of developing various malignancies, most of which are m yeloid disorders. The observed loss of NF1 allele in the myeloid malig nancies of NF1 patients suggests a role of NF1 as a tumor suppressor g ene. Loss of 17p was found to be quite frequent in neural crest tumors from patients with NF1, raising the possibility of p53 tumor suppress or gene involvement in other NF1-related tumors.METHODS, The authors s tudied mutations in the NF1 and p53 genes, using loss of heterozygosit y, single strand conformation polymorphism, heteroduplex and sequencin g analyses. RESULTS. An NF1 germline mutation was identified in exon 3 1 of a child who developed juvenile chronic myelogenous leukemia (JCML ). The mutation was segregated within the proband's family. A 14bp del etion at exon 6 of the p53 gene was observed when JCML was diagnosed, and the wild-type p53 allele was lost during progression of the diseas e. No loss of the normal NF1 allele could be detected. CONCLUSIONS, A germline mutation in the NF1 gene and sequential inactivation of p53 a lleles in the malignant clone of JCML raise the possibility of a corre lation between NF1 and p53 genes in the tumorigenesis of JCML. (C) 199 7 American Cancer Society.