PHOX2B mutations and genetic predisposition to neuroblastoma

Patrizia Perri, Tiziana Bachetti, Luca Longo, Ivana Matera, Marco Seri, Gian Paolo Tonini, Isabella Ceccherini

Research output: Contribution to journalArticlepeer-review


Neuroblastoma (NB) is a childhood malignancy originating from neural crest cells, which seldom occurs in association with other neurocristopathies. Owing to the rarity of familial NB cases, only a few linkage data are available and no mutations in candidate genes have been demonstrated up till now. Germline mutations in a small proportion of NB patients have been recently reported in the paired-like homeobox 2B (PHOX2B) gene, suggesting its role in NB predisposition. On the basis of this indication, we screened three Italian families with recurrence of NB and one family with occurrence of ganglioneuroblastoma and isolated Hirschsprung disease for PHOX2B defects. Our analysis did not show any mutation, excluding PHOX2B as the NB susceptibility gene in the families we analysed. Our findings combined with those derived from other PHOX2B mutation screenings and from genome-wide linkage analysis support a remarkable genetic heterogeneity of NB and suggest an oligogenic model of disease transmission. Furthermore, as PHOX2B mutations were mainly observed in some NB families with multifocal and syndromic NB, features that are missing in the families we have studied, we suggest they represent second-site modifications responsible for a specific phenotype rather than causal mutations of a major locus.

Original languageEnglish
Pages (from-to)3050-3053
Number of pages4
Issue number18
Publication statusPublished - Apr 21 2005


  • Cancer predisposition
  • Familial neuroblastoma
  • Oligogenic model
  • PHOX2B

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics


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