Discovery and characterization of a novel CCND1/MRCK gene fusion in mantle cell lymphoma.
Chioniso Patience MasamhaTodd R AlbrechtEric J WagnerPublished in: Journal of hematology & oncology (2016)
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.
Keyphrases
- cell cycle
- cancer therapy
- binding protein
- copy number
- poor prognosis
- genome wide
- small molecule
- cell therapy
- protein kinase
- gene expression
- tyrosine kinase
- early onset
- stem cells
- genetic diversity
- mesenchymal stem cells
- dna methylation
- free survival
- dna binding
- long non coding rna
- drug induced
- duchenne muscular dystrophy
- pi k akt
- hyaluronic acid