Homozygous inactivation of NF1 gene in a patient with familial NF1 and disseminated neuroblastoma

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. -->

ISSN:	1552-4825
Přístupová URL adresa:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2fd1dfa81a90c60ac65ac0bf2fb47d3 https://pubmed.ncbi.nlm.nih.gov/12687660
Rights:	CLOSED
Přírůstkové číslo:	edsair.doi.dedup.....e2fd1dfa81a90c60ac65ac0bf2fb47d3
Autor:	Katia Mazzocco, Gian Paolo Tonini, Bruno De Bernardi, Crocifissa Lo Cunsolo, Raffaella Defferrari, Paola Origone
Rok vydání:	2003
Předmět:	Male congenital hereditary and neonatal diseases and abnormalities Neurofibromatosis 1 Biology medicine.disease_cause Germline Neuroblastoma Germline mutation Fatal Outcome medicine Gene silencing Humans Point Mutation Gene Silencing Neurofibromatosis neoplasms Genetics (clinical) In Situ Hybridization Fluorescence Polymorphism Single-Stranded Conformational Genetics Mutation Reverse Transcriptase Polymerase Chain Reaction Point mutation Liver Neoplasms medicine.disease eye diseases nervous system diseases Tumor progression Chromosomes Human Pair 1 Child Preschool Cancer research Bone Marrow Neoplasms Gene Deletion
Zdroj:	American journal of medical genetics. Part A. (4)
ISSN:	1552-4825
Popis:	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 cafe-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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2fd1dfa81a90c60ac65ac0bf2fb47d3 https://pubmed.ncbi.nlm.nih.gov/12687660 Zobrazit plný text záznamu Plný text