c.1810C>T polymorphism of NTRK1 gene is associated with reduced survival in neuroblastoma patients.
BMC Cancer
; 9: 436, 2009 Dec 13.
Article
em En
| MEDLINE
| ID: mdl-20003389
ABSTRACT
BACKGROUND:
TrkA (encoded by NTRK1 gene), the high-affinity tyrosine kinase receptor for neurotrophins, is involved in neural crest cell differentiation. Its expression has been reported to be associated with a favourable prognosis in neuroblastoma. Therefore, the entire coding sequence of NTRK1 gene has been analysed in order to identify mutations and/or polymorphisms which may alter TrkA receptor expression.METHODS:
DNA was extracted from neuroblastomas of 55 Polish and 114 Italian patients and from peripheral blood leukocytes of 158 healthy controls. Denaturing High-Performance Liquid Chromatography (DHPLC) and Single-Strand Conformation Polymorphism (SSCP) analysis were used to screen for sequence variants. Genetic changes were confirmed by direct sequencing and correlated with biological and clinical data.RESULTS:
Three previously reported and nine new single nucleotide polymorphisms were detected. c.1810C>T polymorphism present in 8.7% of cases was found to be an independent marker of disease recurrence (OR = 13.3; p = 0.009) associated with lower survival rates (HR = 4.45 p = 0.041). c.1810C>T polymorphism's unfavourable prognostic value was most significant in patients under 18 months of age with no MYCN amplification (HR = 26; p = 0.008). In-silico analysis of the c.1810C>T polymorphism suggests that the substitution of the corresponding amino acid residue within the conservative region of the tyrosine kinase domain might theoretically interfere with the functioning of the TrkA protein.CONCLUSIONS:
NTRK1 c.1810C>T polymorphism appears to be a new independent prognostic factor of poor outcome in neuroblastoma, especially in children under 18 months of age with no MYCN amplification.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Receptor trkA
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Polimorfismo de Nucleotídeo Único
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Neuroblastoma
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Child, preschool
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Humans
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Infant
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article