title: Discovery and characterization of a novel CCND1/MRCK gene fusion in mantle cell lymphoma.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Butler University, 4600 Sunset Avenue, Indianapolis, IN, 46208, USA. cmasamha@butler.edu.
authors.forename: Chioniso Patience
authors.identifier: http://orcid.org/0000-0002-2427-786X
authors.initials: CP
authors.lastname: Masamha
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Albrecht
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX, 77555, USA. ejwagner@utmb.edu.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wagner
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D050939:Gene Fusion; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D065636:Myotonin-Protein Kinase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger; D019938:Cyclin D1; C105518:CDC42BPA protein, human; D065636:Myotonin-Protein Kinase
keywords: 3′UTR; Alternative polyadenylation; Cyclin D1; Gene fusion; Mantle cell lymphoma; miRNA