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 language | English |
|---|---|
| Pages (from-to) | 3050-3053 |
| Number of pages | 4 |
| Journal | Oncogene |
| Volume | 24 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - Apr 21 2005 |
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Keywords
- Cancer predisposition
- Familial neuroblastoma
- Oligogenic model
- PHOX2B
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
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 journal › Article
}
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 -