The absence of a novel intron 19-retaining transcript (-I19) and amplification correlates with an excellent clinical outcome in neuroblastoma patients.

ALK missense mutations are detected in 8% of neuroblastoma (NB) tumors at diagnosis and confer gain-of-function oncogenic effects. The mechanisms by which the expression of wild-type or mutant , which is detectable in the majority of cases, is regulated are not well understood. We have identified a novel transcript characterized by the retention of intron 19 (). was detected in 4/4 NB cell lines, but not other non-NB cells with aberrations. The functional significance of was determined by specific siRNA knockdown of this transcript, which resulted in substantially decreased expression of the fully-spliced transcripts (FS-) and a significant reduction in cell growth. We also demonstrate that is a precursor of FS-. was detected in 14/37 (38%) tumors from patients with newly diagnosed NB. expression correlated with undifferentiated histology and strong protein expression detectable by immunohistochemistry. Importantly, patients with tumors that did not express and lacked MYCN amplification had an excellent clinical outcome, with 19/19 patients survived at 5-years. In conclusion, is a novel transcript that likely represents a marker of undifferentiated NB cells. The absence of and amplification is a useful prognostic marker for NB patients.