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Lookup NU author(s): Dr Lindsay Nicholson,
Dr Simon BomkenORCiD,
Professor Hermann Josef Vormoor,
Dr Andrew Hall,
Professor Julie Irving
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Casitas B-lineage lymphoma (CBL) proteins are RING finger ubiquitin E3 ligases that attenuate the signaling of receptor tyrosine kinases and are mutated in a number of myeloid disorders. In this study, mutational screening of the linker-RING domains of CBL and CBLB was performed by denaturing high performance liquid chromatography in a cohort of diagnostic (n = 180) or relapse (n = 46) samples from children with acute lymphoblastic leukemia. Somatic mutations were identified in three children, giving an overall incidence of 1.7% and involved small deletions affecting the intron/exon boundaries of exon 8, leading to skipping of exon 8 and abolishing E3 ligase function. Mutated primary samples were associated with constitutive activation of the RAS pathway and sensitivity to MEK inhibitors was shown. Thus, mutation of CBL is an alternative route to activate the RAS pathway and may identify children who are candidates for MEK inhibitor clinical trials. (c) 2011 Wiley Periodicals, Inc.
Author(s): Nicholson L, Knight T, Matheson E, Minto L, Case M, Sanichar M, Bomken S, Vormoor J, Hall A, Irving J
Publication type: Article
Publication status: Published
Journal: Genes, Chromosomes & Cancer
Print publication date: 10/11/2011
ISSN (print): 1045-2257
ISSN (electronic): 1098-2264
Publisher: John Wiley & Sons, Inc.
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