ALK germline mutations in patients with neuroblastoma: a rare and weakly penetrant syndrome.
Eur J Hum Genet
; 20(3): 291-7, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22071890
ABSTRACT
Neuroblastic tumours may occur in a predisposition context. Two main genes are involved PHOX2B, observed in familial cases and frequently associated with other neurocristopathies (Ondine's and Hirschsprung's disease); and ALK, mostly in familial tumours. We have assessed the frequency of mutations of these two genes in patients with a presumable higher risk of predisposition. We sequenced both genes in 26 perinatal cases (prebirth and <1 month of age, among which 10 were multifocal), 16 multifocal postnatal (>1 month) cases, 3 pairs of affected relatives and 8 patients with multiple malignancies. The whole coding sequences of the two genes were analysed in tumour and/or constitutional DNAs. We found three ALK germline mutations, all in a context of multifocal tumours. Two mutations (T1151R and R1192P) were inherited and shared by several unaffected patients, thus illustrating an incomplete penetrance. Younger age at tumour onset did not seem to offer a relevant selection criterion for ALK analyses. Conversely, multifocal tumours might be the most to benefit from the genetic screening. Finally, no PHOX2B germline mutation was found in this series. In conclusion, ALK deleterious mutations are rare events in patients with a high probability of predisposition. Other predisposing genes remain to be discovered.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Proteína Tirosina Quinases
/
Mutação em Linhagem Germinativa
/
Neoplasias Primárias Múltiplas
/
Neuroblastoma
Tipo de estudo:
Diagnostic_studies
Limite:
Female
/
Humans
/
Infant
/
Male
/
Newborn
Idioma:
En
Revista:
Eur J Hum Genet
Ano de publicação:
2012
Tipo de documento:
Article