| Summary: | <p>Abstract</p> <p>Background</p> <p>TrkA (encoded by <it>NTRK1 </it>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 <it>NTRK1 </it>gene has been analysed in order to identify mutations and/or polymorphisms which may alter TrkA receptor expression.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 <it>MYCN </it>amplification (HR = 26; p = 0.008). <it>In-silico </it>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.</p> <p>Conclusions</p> <p><it>NTRK1 </it>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 <it>MYCN </it>amplification.</p>
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