title: Loss of NF1 alleles in phaeochromocytomas from patients with type I neurofibromatosis.
abstract: Type I neurofibromatosis (NF1) is a common autosomal dominant disorder that affects tissues derived from the neural crest. The manifestations are varied, comprising generalised disorders of growth and development as well as an increased risk of benign and malignant tumours including phaeochromocytomas and neurofibrosarcomas. The NF1 locus has been mapped to chromosome bands 17q11-12, and recently the NF1 gene has been cloned. Deletions identified in the constitutional genotype of some patients have suggested that the NF1 phenotype may arise from loss of function mutations of the NF1 gene, consistent with the hypothesis that it is a tumour suppressor gene. To date, however, analysis of NF1 tumours has not revealed the frequent allele losses encompassing the NF1 locus, implying loss of the wild-type NF1 allele, which would support this hypothesis. We report allele losses with markers flanking the NF1 region in each of 7 NF1 phaeochromocytomas. In each of the 3 tumours for which this could be determined, the loss involved the wild-type chromosome. These results provide strong evidence that, in cells of the adrenal medulla at least, the NFI gene may act as a tumour suppressor.
authors.affiliation: Department of Pathology, University of Cambridge, United Kingdom.
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: M A
authors.initials: MA
authors.lastname: Ponder
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: B A
authors.initials: BA
authors.lastname: Smith
authors.forename: C G
authors.initials: CG
authors.lastname: Mathew
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000235:genetics*; D000483:Alleles; D015139:Blotting, Southern; D002886:Chromosomes, Human, Pair 17; D015342:DNA Probes / Q000235:genetics; D005260:Female; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics*; D006801:Humans; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000235:genetics; D010375:Pedigree; D010673:Pheochromocytoma / Q000150:complications / Q000235:genetics*
chemical_list: D015342:DNA Probes