title: Rare occurrence of PHOX2b mutations in sporadic neuroblastomas.
abstract: Neuroblastomas (NBs) are frequent solid tumors in childhood for which no specific genetic marker linked to their development has been identified to date. PHOX2b, which regulates the autonomic neuron development, has been associated with the development of autonomic diseases, and has been considered a potential candidate gene for neural crest-derived tumors such as NB. To ascertain the role of the PHOX2b gene in NB development, we have sequenced the complete PHOX2b coding region in tumors from 69 patients with sporadic NB, while 130 blood donors served as negative controls and 9 NB cell lines as positive controls. We found a missense deletion in exon 3 in a cell line. A further silent mutation in exon 3 (c.870C>A) was observed in 3 tumors but in none of the controls. A new polymorphism in intron 1 (IVS1-114 G>A) was observed in 31 tumor samples (44.9%) and in 68 controls (52.3%). We did not find any conclusive association of the polymorphisms or mutations in PHOX2b with the development of NB, although the large confidence intervals neither substantiate nor exclude a role for this gene in the tumor etiology.
authors.affiliation: Department of Pediatric Surgery, Technische Universität Dresden, Dresden, Germany. Alexandre.serra@uniklinikum-dresden.de
authors.forename: Alexandre
authors.initials: A
authors.lastname: Serra
authors.forename: Beate
authors.initials: B
authors.lastname: Häberle
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Roland
authors.initials: R
authors.lastname: Kappler
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
authors.forename: Dietmar
authors.initials: D
authors.lastname: Roesner
authors.forename: Guido
authors.initials: G
authors.lastname: Fitze
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics*; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors