Coexpression of mRNA for the full-length neurotrophin receptor trk-C and trk-A in favourable neuroblastoma

T Svensson, M Ryden, FH Schilling, C Dominici… - European Journal of …, 1997 - Elsevier
T Svensson, M Ryden, FH Schilling, C Dominici, R Sehgal, CF Ibanez, P Kogner
European Journal of Cancer, 1997Elsevier
Neuroblastoma, a childhood tumour of the sympathetic nervous system, may sometimes
regress spontaneously in infants, or progress to a poor clinical outcome despite intensive
therapy. Neuroblastomas express neurotrophin receptors and high levels of mRNA for trk-A
correlates with favourable outcome, whereas trk-B mRNA is expressed by more
unfavourable tumours. Using a sensitive RNase protection assay, mRNA expression for the
neurotrophin receptor trk-C was investigated in 50 tumour samples from 45 children at …
Neuroblastoma, a childhood tumour of the sympathetic nervous system, may sometimes regress spontaneously in infants, or progress to a poor clinical outcome despite intensive therapy. Neuroblastomas express neurotrophin receptors and high levels of mRNA for trk-A correlates with favourable outcome, whereas trk-B mRNA is expressed by more unfavourable tumours. Using a sensitive RNase protection assay, mRNA expression for the neurotrophin receptor trk-C was investigated in 50 tumour samples from 45 children at different stages including metastatic and relapsing tumour tissue, out of which 22 were also investigated for trk-A mRNA. Thirty-seven of 43 primary tumours (86%) showed trk-C mRNA with more than 300-fold difference between the highest and the lowest values. A higher trk-C index (trk-C mRNA/GAPDH mRNA) was associated with favourable features such as younger age (P=0.009–0.003), favourable tumour stage (1, 2 or 4S; P<0.001) and favourable prognosis (P=0.044). Better survival probability was shown in children with intermediate or high trk-C index compared with patients with low or undetectable levels (P=0.031). All localised tumours co-expressed mRNA for trk-A and trk-C receptors. RT–PCR analysis detected mRNA encoding the cytoplasmic trk-C tyrosine kinase region only in favourable neuroblastomas. We conclude that favourable neuroblastoma may express the full-length trk-C receptor while unfavourable tumours, especially those with MYCN amplification, seem to either express no trk-C or truncated trk-C receptors with unknown biological function. Trk-C and possibly its preferred ligand NT-3 may be involved in the biology of favourable neuroblastomas showing apoptosis or differentiation.
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