title: Mantle cell lymphoma with a novel t(11;12)(q13;p11.2): a proposed alternative mechanism of CCND1 up-regulation.
abstract: Mantle cell lymphoma (MCL) is typically characterized by t(11;14), which places the IGH@ enhancer elements upstream of CCND1. This fusion results in up-regulation of CCND1 and consequently its protein product cyclin D1. Recent studies have shown that in MCL, mutations or translocations occurring within the 3' untranslated region (UTR) of the CCND1 gene can result in a truncated mRNA transcript that is more stable and associated with more aggressive disease. We identified a case of MCL showing cyclin D1 overexpression by immunohistochemistry and a t(11;12)(q13;p11.2) by conventional cytogenetic studies. Next-generation genomic sequencing indicated a chromosomal break through the CCND1 3'-UTR and fusion with a non-coding region of chromosome 12. We suggest that, in the absence of the typical CCND1/IGH@ fusion, this rearrangement promotes MCL pathogenesis by eliminating miRNA interaction elements within the 3'-UTR of the CCND1 mRNA transcript consequently resulting in CCND1 overexpression.
authors.affiliation: Department of Pathology, University of California, San Francisco, CA 94143.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Menke
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester MN 55905.
authors.forename: George
authors.initials: G
authors.lastname: Vasmatzis
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester MN 55905.
authors.forename: Stephen
authors.initials: S
authors.lastname: Murphy
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester MN 55905.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, Mayo Clinic, Jacksonville, FL 32224.
authors.forename: David M
authors.initials: DM
authors.lastname: Menke
authors.affiliation: Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL 32224.
authors.forename: Han W
authors.initials: HW
authors.lastname: Tun
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN 55905.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: King
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN 55905.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Smoley
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN 55905.
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN 55905. Electronic address: Sukov.william@mayo.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Sukov
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D019938:Cyclin D1 / Q000032:analysis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D020522:Lymphoma, Mantle-Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D014178:Translocation, Genetic; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D019938:Cyclin D1
keywords: 3′-UTR; CCND1; Cytogenetics; Mantle cell lymphoma; Mate-pair sequencing; Translocation; microRNA