PXD021792

PXD021792 is an original dataset announced via ProteomeXchange.

Title	Proteomics and phosphoproteomics on NB1 and IMR32 neuroblastoma cells stimulated with ALAKAL2
Description	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.
HostingRepository	PRIDE
AnnounceDate	2020-11-25
AnnouncementXML	Submission_2020-11-24_22:25:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Proteomics Core Facility
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-02 04:16:40	ID requested
⏵ 1	2020-11-24 22:25:44	announced

Dataset with its publication pending

submitter keyword: ALKAL2, neuroblastoma, NB, cancer, Anaplastic Lymphoma Kinase, ALK, tandem mass tag, TMT, phosphorylation

Ruth H. Palmer
contact affiliation	Professor, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden
contact email	ruth.palmer@gu.se
lab head
Proteomics Core Facility
contact affiliation	SAMBIO Core Facilities, Sahgrenska Academy, University of Gothenburg
contact email	gupcf@outlook.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/11/PXD021792

PRIDE project URI

• PRIDE
  1. PXD021792
     1. Label: PRIDE project
     2. Name: Proteomics and phosphoproteomics on NB1 and IMR32 neuroblastoma cells stimulated with ALAKAL2