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

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

doi:10.1186/s13045-016-0260-7

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

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

Biochemistry & Molecular Biology

Research output: Contribution to journal › Article › peer-review

7 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 language	English (US)
Article number	30
Journal	Journal of Hematology and Oncology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s13045-016-0260-7
State	Published - 2016

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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10.1186/s13045-016-0260-7

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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.",

keywords = "3'UTR, Alternative polyadenylation, Cyclin D1, Gene fusion, Mantle cell lymphoma, MiRNA",

author = "Masamha, {Chioniso Patience} and Albrecht, {Todd R.} and Wagner, {Eric J.}",

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AU - Masamha, Chioniso Patience

AU - Albrecht, Todd R.

AU - Wagner, Eric J.

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Y1 - 2016

N2 - 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.

AB - 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.

KW - 3'UTR

KW - Alternative polyadenylation

KW - Cyclin D1

KW - Gene fusion

KW - Mantle cell lymphoma

KW - MiRNA

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

Abstract

Keywords

ASJC Scopus subject areas

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