An alternative transcript of MYCNOS, MYCNOS-01, post-transcriptionally regulates MYCN levels and affects growth in MYCN-amplified rhabdomyosarcoma and neuroblastoma cells.
Building on previous work, an inducible model in human myoblast cells was used to show that PAX3-FOXO1 and MYCN can initiate rhabdomyosarcoma development but, contrary to current thinking, tumour recurrences occasionally arose independent of the fusion protein.
Following intramuscular injection into immunodeficient mice, myoblasts expressing PAX3-FOXO1 and MYCN formed rapidly growing RMS tumours, whereas myoblasts expressing only PAX3-FOXO1 formed tumours after a longer latency period.
MYCN is a transcription factor that is expressed during the development of the neural crest and its dysregulation plays a major role in the pathogenesis of pediatric cancers such as neuroblastoma, medulloblastoma and rhabdomyosarcoma.
Using quantitative polymerase chain reaction, we measured MYCN copy number and expression levels in rhabdomyosarcoma samples from 113 and 92 individuals with a confirmed diagnosis of rhabdomyosarcoma, respectively.
These data suggest that MYCN expression is a common feature of rhabdomyosarcoma, independent of gene amplification and without a clear relationship with specific histological and clinical features.
So far no continuous RMS cell line carrying the t(1;13)(p36;q14) has been described, and PAX7-FKHR and MYCN amplifications have always been reported to occur separately in rhabdomyosarcoma (RMS).
All three RMS cell lines, including FU-MMT-3, showed amplification of the c-myc gene (approximately fourfold to eightfold), while no cell lines demonstratedMYCN gene amplification.
The findings are compatible with previous studies that demonstrated cytogenetic evidence of gene amplification in RMS, and help to clarify conflicting reports in the literature about MYCN amplification in alveolar and embryonal RMS.