Proteomics and phosphoproteomics on NB1 and IMR32 neuroblastoma cells stimulated with ALAKAL2

ABSTRACT: High-risk neuroblastoma (NB) is notoriously difficult to treat and is responsible for a disproportionate number of childhood deaths due to cancer. One long accepted indicator of high-risk NB and poor prognosis is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable in this patient population. The identification of Anaplastic Lymphoma Kinase (ALK) as an oncogene in NB raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in the treatment of NB patients who harbor activating ALK mutations. The number of ALK-positive NB patients on primary diagnosis is in the range of 8-10%, a figure that increases substantially in the relapsed patient population. ALK signaling is activated by the ALKAL2 ligand located on the distal portion of chromosome 2, along with the ALK receptor and MYCN loci, in the ‘2p gain’ region that has been associated with NB. The question of whether dysregulation of ALK ligand may also play a role in NB has not been addressed, although notably, one of the first oncogenes described was the v-sis oncogene that shares more than 90% homology with the PDGF ligand. Therefore, we tested whether ALKAL ligand was able to potentiate NB progression in the absence of ALK mutation. We show here that overexpression of ALKAL2 is sufficient to drive rapid onset and penetrant Th-MYCN driven NB in the absence of ALK mutation, and that these tumours are sensitive to ALK TKI therapy. These results suggest that additional NB patients, such as those exhibiting 2p gain, may also benefit from ALK TKI based therapeutic intervention.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Neuroblastoma Cell

DISEASE(S): Neuroblastoma

SUBMITTER: Proteomics Core Facility  

LAB HEAD: Ruth H. Palmer

PROVIDER: PXD021792 | Pride | 2020-11-25

REPOSITORIES: Pride