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

J Hematol Oncol. 2016 Mar 29:9:30. doi: 10.1186/s13045-016-0260-7.

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.

Keywords: 3′UTR; Alternative polyadenylation; Cyclin D1; Gene fusion; Mantle cell lymphoma; miRNA.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • Cyclin D1 / genetics*
  • Cyclin D1 / metabolism
  • Gene Fusion*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Introns / genetics
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / metabolism
  • Lymphoma, Mantle-Cell / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Myotonin-Protein Kinase / genetics*
  • Myotonin-Protein Kinase / metabolism
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • RNA, Messenger
  • Cyclin D1
  • CDC42BPA protein, human
  • Myotonin-Protein Kinase