Discovery and characterization of a novel CCND1/MRCK gene fusion in mantle cell lymphoma

被引:8
作者
Masamha, Chioniso Patience [1 ]
Albrecht, Todd R. [2 ]
Wagner, Eric J. [2 ]
机构
[1] Butler Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, 4600 Sunset Ave, Indianapolis, IN 46208 USA
[2] Univ Texas Med Branch, Dept Biochem & Mol Biol, 301 Univ Blvd, Galveston, TX 77555 USA
基金
美国国家卫生研究院;
关键词
Mantle cell lymphoma; Gene fusion; Cyclin D1; miRNA; Alternative polyadenylation; 3 ' UTR; MESSENGER-RNA;
D O I
10.1186/s13045-016-0260-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The t(11; 14) translocation resulting in constitutive cyclin D1 expression is an early event in mantle cell lymphoma (MCL) transformation. Patients with a highly proliferative phenotype produce cyclin D1 transcripts with truncated 3'UTRs that evade miRNA regulation. Here, we report the recurrence of a novel gene fusion in MCL cell lines and MCL patient isolates that consists of the full protein coding region of cyclin D1 (CCND1) and a 3'UTR consisting of sequences from both the CCND1 3'UTR and myotonic dystrophy kinase-related Cdc42-binding kinase's (MRCK) intron one. The resulting CCND1/MRCK mRNA is resistant to CCND1-targeted miRNA regulation, and targeting the MRCK region of the chimeric 3'UTR with siRNA results in decreased CCND1 levels.
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页数:5
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