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

Chioniso Patience Masamha, Todd R. Albrecht, Eric J. Wagner

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    5 Scopus citations

    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.

    Original languageEnglish (US)
    Article number30
    JournalJournal of Hematology and Oncology
    Volume9
    Issue number1
    DOIs
    StatePublished - Jan 1 2016

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    Keywords

    • 3'UTR
    • Alternative polyadenylation
    • Cyclin D1
    • Gene fusion
    • Mantle cell lymphoma
    • MiRNA

    ASJC Scopus subject areas

    • Molecular Biology
    • Hematology
    • Oncology
    • Cancer Research

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