We identified novel ALK fusions in a neuroblastoma (BEND5-ALK) and an astrocytoma (PPP1CB-ALK), novel BRAF fusions in an astrocytoma (BCAS1-BRAF) and a ganglioglioma (TMEM106B-BRAF), and a novel PAX3-GLI2 fusion in a rhabdomyosarcoma.
Over the last few years, studies have demonstrated the occurrence of autophagy in different Anaplastic Lymphoma Kinase (ALK)-associated cancers, notably ALK-positive anaplastic large cell lymphoma (ALCL), non-small cell lung carcinoma (NSCLC), Neuroblastoma (NB), and Rhabdomyosarcoma (RMS).
Here, we report that LDK378 reduces cell viability and induces cell death in RMS cell lines at low micromolar IC50 concentrations irrespective of ALK expression levels or phosphorylation status.
In vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival.
Quantitative assessment of ALK mRNA expression helps to improve risk stratification of RMS patients and identifies tumours with adverse biological characteristics and aggressive behaviour.
Although it remains controversial whether ALK expression without gene rearrangement is therapeutically relevant, this comprehensive analysis may help future studies on the utility of ALK-targeted therapy for patients with rhabdomyosarcoma.
We also identified possible application of an ALK inhibitor to RMS, as ALK amplification and frequent expression of ALK were detected in our RMS cohort.