@article{abe1733161ce4eccaa5c64fc8cc69044,
title = "ALK ligand ALKAL2 potentiates MYCN-driven neuroblastoma in the absence of ALK mutation",
abstract = "High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer. One indicator of high-risk NB is amplification of the neural MYC (MYCN) oncogene, which is currently therapeutically intractable. Identification of anaplastic lymphoma kinase (ALK) as an NB oncogene raised the possibility of using ALK tyrosine kinase inhibitors (TKIs) in treatment of patients with activating ALK mutations. 8–10% of primary NB patients are ALK-positive, a figure that increases in the relapsed population. ALK is activated by the ALKAL2 ligand located on chromosome 2p, along with ALK and MYCN, in the “2p-gain” region associated with NB. Dysregulation of ALK ligand in NB has not been addressed, although one of the first oncogenes described was v-sis that shares > 90% homology with PDGF. Therefore, we tested whether ALKAL2 ligand could potentiate NB progression in the absence of ALK mutation. We show that ALKAL2 overexpression in mice drives ALK TKI-sensitive NB in the absence of ALK mutation, suggesting that additional NB patients, such as those exhibiting 2p-gain, may benefit from ALK TKI-based therapeutic intervention.",
keywords = "2p-gain, ALK, ALKAL, MYCN, neuroblastoma",
author = "Marcus Boren{\"a}s and Ganesh Umapathy and Wei-Yun Lai and Lind, {Dan E.} and Barbara Witek and Jikui Guan and Patricia Mendoza-Garcia and Tafheem Masudi and Arne Claeys and Tzu-Po Chuang and {el Wakil}, Abeer and Badrul Arefin and Susanne Fransson and Jan Koster and Mathias Johansson and Jennie Gaarder and {van den Eynden}, Jimmy and Bengt Hallberg and Palmer, {Ruth H.}",
note = "Funding Information: The authors thank Anne Uv for critical comments on the manuscript. The authors would like to acknowledge support of Science for Life Laboratory/Clinical Genomics, Gothenburg, for providing assistance in computational infrastructure and of the National Genomics Infrastructure (NGI)/Science for Life Laboratory, Stockholm, for performing massive parallel sequencing. Work performed at NGI has been funded by RFI/VR and Science for Life Laboratory, Sweden. Quantitative proteomics analysis was performed by Evelin Berger at the Proteomics Core Facility of Sahlgrenska Academy, University of Gothenburg. This work has been supported by grants from the Swedish Cancer Society (RHP CAN18/729; BH: CAN18/718), the Swedish Childhood Cancer Foundation (RHP:PR2015-0096; SF:NCp2015-0061 and PR2018-0099; JG TJ2016-0088 and PR2016-2011; GU: TJ2018-0056; BH: PR2017-0110), the Swedish Research Council (RHP 2015-04466; BH:2017-01324), the Swedish Foundation for Strategic Research (RB13-0204), the G?ran Gustafsson Foundation (RHP2016), a Ghent University Special Research Fund Starting Grant (JVdE: BOF.STG.2019.0073.01), G?teborgs L?kare S?llskap (MB) and the Knut and Alice Wallenberg Foundation (KAW 2018.0057). Funding Information: The authors thank Anne Uv for critical comments on the manuscript. The authors would like to acknowledge support of Science for Life Laboratory/Clinical Genomics, Gothenburg, for providing assistance in computational infrastructure and of the National Genomics Infrastructure (NGI)/Science for Life Laboratory, Stockholm, for performing massive parallel sequencing. Work performed at NGI has been funded by RFI/VR and Science for Life Laboratory, Sweden. Quantitative proteomics analysis was performed by Evelin Berger at the Proteomics Core Facility of Sahlgrenska Academy, University of Gothenburg. This work has been supported by grants from the Swedish Cancer Society (RHP CAN18/729; BH: CAN18/718), the Swedish Childhood Cancer Foundation (RHP:PR2015‐0096; SF:NCp2015‐0061 and PR2018‐0099; JG TJ2016‐0088 and PR2016‐2011; GU: TJ2018‐0056; BH: PR2017‐0110), the Swedish Research Council (RHP 2015‐04466; BH:2017‐01324), the Swedish Foundation for Strategic Research (RB13‐0204), the G{\"o}ran Gustafsson Foundation (RHP2016), a Ghent University Special Research Fund Starting Grant (JVdE: BOF.STG.2019.0073.01), G{\"o}teborgs L{\"a}kare S{\"a}llskap (MB) and the Knut and Alice Wallenberg Foundation (KAW 2018.0057). Publisher Copyright: {\textcopyright} 2021 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2021",
month = feb,
day = "1",
doi = "https://doi.org/10.15252/embj.2020105784",
language = "English",
volume = "40",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "3",
}