title: Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma.
abstract: Neuroblastoma (NB) is a frequent pediatric tumor for which recurrent somatic rearrangements are known. Germline mutations of predisposing gene(s) are suspected on the basis of rare familial cases and the association of NB with other genetically determined congenital malformations of neural crest-derived cells--namely, Hirschsprung disease (HSCR) and/or congenital central hypoventilation syndrome (CCHS). We recently identified the paired-like homeobox 2B (PHOX2B) gene as the major disease-causing gene in isolated and syndromic CCHS, which prompted us to regard it as a candidate gene in NB. Here, we report on germline mutations of PHOX2B in both a familial case of NB and a patient with the HSCR-NB association. PHOX2B, therefore, stands as the first gene for which germline mutations predispose to NB.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, and Département de Génétique, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Trochet
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.forename: Isabelle
authors.initials: I
authors.lastname: Janoueix-Lerosey
authors.forename: Anne
authors.initials: A
authors.lastname: Deville
authors.forename: Loïc
authors.initials: L
authors.lastname: de Pontual
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
authors.forename: Carole
authors.initials: C
authors.lastname: Coze
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
mesh_terms: D001483:Base Sequence; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors