title: The spectrum of somatic and germline NF1 mutations in NF1 patients with spinal neurofibromas.
abstract: Neurofibromatosis type 1 (NF1) is a common inherited complex multi-system disorder associated with the growth of various benign and malignant tumors. About 40% of NF1 patients develop spinal tumors, of whom some have familial spinal neurofibromatosis (FSNF), a variant form of NF1 in which patients present with multiple bilateral spinal tumors but have few other clinical features of the disease. We have studied 22 spinal neurofibromas derived from 14 unrelated NF1 patients. Seven of these patients satisfied the diagnostic criteria of NF1 while the remaining seven had only few features of NF1. The latter group defined as FSNF harbored significantly higher number of missense or missense and splice-site germline mutations compared to the group with classical NF1. This is the first study to describe NF1 somatic mutations in spinal neurofibromas. Loss-of-heterozygosity (LOH) was identified in 8/22 of the spinal tumors, 75% of LOH observed was found to result from mitotic recombination, suggesting that this may represent a frequent mutational mechanisms in these benign tumors. No evidence for LOH of the TP53 gene was found in these tumors.
authors.affiliation: Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff Cf144XN, UK. Upadhyaya@cardiff.ac.uk
authors.forename: Meena
authors.initials: M
authors.lastname: Upadhyaya
authors.forename: Gill
authors.initials: G
authors.lastname: Spurlock
authors.forename: Lan
authors.initials: L
authors.lastname: Kluwe
authors.forename: Nadia
authors.initials: N
authors.lastname: Chuzhanova
authors.forename: Emma
authors.initials: E
authors.lastname: Bennett
authors.forename: Nick
authors.initials: N
authors.lastname: Thomas
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
authors.forename: Victor
authors.initials: V
authors.lastname: Mautner
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009455:Neurofibroma / Q000235:genetics / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000473:pathology; D013125:Spinal Neoplasms / Q000235:genetics / Q000473:pathology; D055815:Young Adult