C.1810C>T polymorphism of NTRK1 Gene is associated with reduced survival in neuroblastoma patients

Beata S. Lipska, Elzbieta Drozynska, Paola Scaruffi, Gian P. Tonini, Ewa Izycka-Świeszewska, Szymon Zietkiewicz, Anna Balcerska, Danuta Perek, Alicja Chybicka, Wojciech Biernat, Janusz Limon

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number436
JournalBMC Cancer
Volume9
DOIs
Publication statusPublished - Dec 13 2009

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Neuroblastoma
Survival
trkA Receptor
Genes
Neural Crest
Nerve Growth Factors
Receptor Protein-Tyrosine Kinases
Amino Acid Substitution
Computer Simulation
Protein-Tyrosine Kinases
Single Nucleotide Polymorphism
Cell Differentiation
Leukocytes
Survival Rate
High Pressure Liquid Chromatography
Recurrence
Mutation
DNA
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

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Lipska, B. S., Drozynska, E., Scaruffi, P., Tonini, G. P., Izycka-Świeszewska, E., Zietkiewicz, S., ... Limon, J. (2009). C.1810C>T polymorphism of NTRK1 Gene is associated with reduced survival in neuroblastoma patients. BMC Cancer, 9, [436]. https://doi.org/10.1186/1471-2407-9-436

C.1810C>T polymorphism of NTRK1 Gene is associated with reduced survival in neuroblastoma patients. / Lipska, Beata S.; Drozynska, Elzbieta; Scaruffi, Paola; Tonini, Gian P.; Izycka-Świeszewska, Ewa; Zietkiewicz, Szymon; Balcerska, Anna; Perek, Danuta; Chybicka, Alicja; Biernat, Wojciech; Limon, Janusz.

In: BMC Cancer, Vol. 9, 436, 13.12.2009.

Research output: Contribution to journalArticle

Lipska, BS, Drozynska, E, Scaruffi, P, Tonini, GP, Izycka-Świeszewska, E, Zietkiewicz, S, Balcerska, A, Perek, D, Chybicka, A, Biernat, W & Limon, J 2009, 'C.1810C>T polymorphism of NTRK1 Gene is associated with reduced survival in neuroblastoma patients', BMC Cancer, vol. 9, 436. https://doi.org/10.1186/1471-2407-9-436
Lipska BS, Drozynska E, Scaruffi P, Tonini GP, Izycka-Świeszewska E, Zietkiewicz S et al. C.1810C>T polymorphism of NTRK1 Gene is associated with reduced survival in neuroblastoma patients. BMC Cancer. 2009 Dec 13;9. 436. https://doi.org/10.1186/1471-2407-9-436
Lipska, Beata S. ; Drozynska, Elzbieta ; Scaruffi, Paola ; Tonini, Gian P. ; Izycka-Świeszewska, Ewa ; Zietkiewicz, Szymon ; Balcerska, Anna ; Perek, Danuta ; Chybicka, Alicja ; Biernat, Wojciech ; Limon, Janusz. / C.1810C>T polymorphism of NTRK1 Gene is associated with reduced survival in neuroblastoma patients. In: BMC Cancer. 2009 ; Vol. 9.
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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.",
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AU - Lipska, Beata S.

AU - Drozynska, Elzbieta

AU - Scaruffi, Paola

AU - Tonini, Gian P.

AU - Izycka-Świeszewska, Ewa

AU - Zietkiewicz, Szymon

AU - Balcerska, Anna

AU - Perek, Danuta

AU - Chybicka, Alicja

AU - Biernat, Wojciech

AU - Limon, Janusz

PY - 2009/12/13

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N2 - 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.

AB - 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.

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