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 journalArticle

38 Citations (Scopus)

Abstract

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
JournalOncogene
Volume24
Issue number18
DOIs
Publication statusPublished - Apr 21 2005

Fingerprint

Homeobox Genes
Genetic Predisposition to Disease
Neuroblastoma
Mutation
Genetic Heterogeneity
Germ-Line Mutation
Neural Crest
Information Storage and Retrieval
Genes
Genome
Phenotype
Recurrence

Keywords

  • Cancer predisposition
  • Familial neuroblastoma
  • Oligogenic model
  • PHOX2B

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Perri, P., Bachetti, T., Longo, L., Matera, I., Seri, M., Tonini, G. P., & Ceccherini, I. (2005). PHOX2B mutations and genetic predisposition to neuroblastoma. Oncogene, 24(18), 3050-3053. https://doi.org/10.1038/sj.onc.1208532

PHOX2B mutations and genetic predisposition to neuroblastoma. / Perri, Patrizia; Bachetti, Tiziana; Longo, Luca; Matera, Ivana; Seri, Marco; Tonini, Gian Paolo; Ceccherini, Isabella.

In: Oncogene, Vol. 24, No. 18, 21.04.2005, p. 3050-3053.

Research output: Contribution to journalArticle

Perri, P, Bachetti, T, Longo, L, Matera, I, Seri, M, Tonini, GP & Ceccherini, I 2005, 'PHOX2B mutations and genetic predisposition to neuroblastoma', Oncogene, vol. 24, no. 18, pp. 3050-3053. https://doi.org/10.1038/sj.onc.1208532
Perri P, Bachetti T, Longo L, Matera I, Seri M, Tonini GP et al. PHOX2B mutations and genetic predisposition to neuroblastoma. Oncogene. 2005 Apr 21;24(18):3050-3053. https://doi.org/10.1038/sj.onc.1208532
Perri, Patrizia ; Bachetti, Tiziana ; Longo, Luca ; Matera, Ivana ; Seri, Marco ; Tonini, Gian Paolo ; Ceccherini, Isabella. / PHOX2B mutations and genetic predisposition to neuroblastoma. In: Oncogene. 2005 ; Vol. 24, No. 18. pp. 3050-3053.
@article{549c11725731413e915bb095e2081067,
title = "PHOX2B mutations and genetic predisposition to neuroblastoma",
abstract = "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.",
keywords = "Cancer predisposition, Familial neuroblastoma, Oligogenic model, PHOX2B",
author = "Patrizia Perri and Tiziana Bachetti and Luca Longo and Ivana Matera and Marco Seri and Tonini, {Gian Paolo} and Isabella Ceccherini",
year = "2005",
month = "4",
day = "21",
doi = "10.1038/sj.onc.1208532",
language = "English",
volume = "24",
pages = "3050--3053",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "18",

}

TY - JOUR

T1 - PHOX2B mutations and genetic predisposition to neuroblastoma

AU - Perri, Patrizia

AU - Bachetti, Tiziana

AU - Longo, Luca

AU - Matera, Ivana

AU - Seri, Marco

AU - Tonini, Gian Paolo

AU - Ceccherini, Isabella

PY - 2005/4/21

Y1 - 2005/4/21

N2 - 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.

AB - 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.

KW - Cancer predisposition

KW - Familial neuroblastoma

KW - Oligogenic model

KW - PHOX2B

UR - http://www.scopus.com/inward/record.url?scp=18344381314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18344381314&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1208532

DO - 10.1038/sj.onc.1208532

M3 - Article

C2 - 15735672

AN - SCOPUS:18344381314

VL - 24

SP - 3050

EP - 3053

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 18

ER -