title: Homozygous inactivation of NF1 gene in a patient with familial NF1 and disseminated neuroblastoma.
abstract: Neurofibromatosis type 1 (NF1) patients are susceptible to tumor development. In the present study we describe a child with NF1 and disseminated neuroblastoma whose death resulted from disease progression. The mother had café-au-lait spots suggesting a familial NF1. Neuroblastoma cells showed MYCN amplification and chromosome 1p36 deletion, common features associated with tumor progression in this malignancy. The NF1 gene displayed a germline T --> C transition of intron 14 in both the proband and mother DNA. This mutation, not yet previously described, occurs in a splicing donor site and produces a new mRNA variant observed together with normal NF1 mRNA. Furthermore, the SSCP analysis of the NF1 gene in tumor cells showed a somatic deletion encompassing the intron 26 and 27b of the paternal NF1 allele. Hence, neuroblastoma cells displayed both somatic and germline mutation of the NF1 gene. Our data suggest that, although rare, neuroblastoma in patients with NF1 may display homozygous gene inactivation.
authors.affiliation: Department of Oncology, Biology and Genetics, University of Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Origone
authors.forename: Raffaella
authors.initials: R
authors.lastname: Defferrari
authors.forename: Katia
authors.initials: K
authors.lastname: Mazzocco
authors.forename: Crocifissa
authors.initials: C
authors.lastname: Lo Cunsolo
authors.forename: Bruno
authors.initials: B
authors.lastname: De Bernardi
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Tonini
mesh_terms: D019046:Bone Marrow Neoplasms / Q000235:genetics*; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D017809:Fatal Outcome; D017353:Gene Deletion; D020868:Gene Silencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction