ALK gene expression

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R-HSA-9725117
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Reaction [BlackBoxEvent]
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Homo sapiens
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18-38% percent of neuroblastomas show amplification of the MYCN gene, while the majority of familial and 10% of sporadic neuroblastomas carry activating mutations in the ALK kinase domain (Mosse et al, 2008; reviewed in Aygun, 2018; Roskoski, 2013). Amplifications of the ALK gene have also been reported in this disease (Caren et al, 2008). ALK and MYCN may play cooperative roles in driving progression of neuroblastoma (Zhu et al, 2012; Mosse et al, 2008; reviewed in Roskoski, 2013).
High levels of ALK expression are seen in MYCN amplified neuroblastomas, and inhibition of ALK activity with tyrosine kinase inhibitors in a MYCN-amplified background reduces proliferation, cell migration and tumor growth in xenograft models, suggesting that ALK activity contributes to the oncogenic potential of MYCN-driven neuroblastomas (Hasan et al, 2013; reviewed in Hallberg and Palmer, 2013).

Literature References
PubMed ID Title Journal Year
18724359 Identification of ALK as a major familial neuroblastoma predisposition gene

Hakonarson, H, Kim, C, Speleman, F, Laureys, G, Mossé, YP, Hou, C, Schork, NJ, Maris, JM, Tonini, GP, Devoto, M, Attiyeh, EF, Rappaport, E, Laudenslager, M, Cole, KA, Wood, A, Lynch, JE, Sennett, R, Laquaglia, MJ, Longo, L, Torkamani, A, Perri, P, Brodeur, GM

Nature 2008
24356251 ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma

Nafady, A, Ohira, M, Nakamura, Y, Akter, J, Hossain, S, Hasan, MK, Ogura, A, Takatori, A, Nakagawara, A, Kadomatsu, K, Suenaga, Y, Kishida, S

Sci Rep 2013
22439933 Activated ALK collaborates with MYCN in neuroblastoma pathogenesis

George, RE, Rodig, SJ, Shin, J, Zhu, S, Helman, D, Kanki, JP, Stewart, RA, Wang, W, Lee, JS, Look, AT, Feng, H, Neuberg, DS, Guo, F, Kutok, JL, Pérez-Atayde, AR

Cancer Cell 2012
18990089 High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours

Abel, F, Carén, H, Kogner, P, Martinsson, T

Biochem J 2008
29380702 Biological and Genetic Features of Neuroblastoma and Their Clinical Importance

Aygun, N

Curr Pediatr Rev 2018
23201355 Anaplastic lymphoma kinase (ALK): structure, oncogenic activation, and pharmacological inhibition

Roskoski, R

Pharmacol. Res. 2013
24060861 Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology

Palmer, RH, Hallberg, B

Nat. Rev. Cancer 2013
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