MicroRNA profiling in ocular adnexal lymphoma: a role for MYC and NFKB1 mediated dysregulation of microRNA expression in aggressive disease

Christoffer Hother, Peter Kristian Rasmussen, Tejal Joshi, Ditte Reker, Ulrik Ralfkiær, Christopher Workman, Steffen Heegaard, Elisabeth Ralfkiær, Kirsten Grønbæk

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Purpose. Ocular adnexal lymphoma (i.e., lymphoma with involvement of the orbit, eyelids, conjunctiva, lacrimal gland, and lacrimal sac), although rare, is common among malignant tumors involving the ocular adnexal region. The main subtypes are low-grade extranodal marginal zone lymphoma (EMZL) and aggressive diffuse large B-cell lymphoma (DLBCL). In rare cases, low-grade EMZL are reported to transform to DLBCL. It is unclear, however, which genetic events distinguish low-grade disease from aggressive, potentially fatal disease.
    Methods. Using LNA-based arrays from Exiqon, we performed global microRNA (miRNA) expression profiling of 18 EMZLs and 25 DLBCLs involving ocular adnexal sites to investigate changes in the miRNA expression in low- versus high-grade disease. Findings were confirmed by real-time quantitative PCR (RTq-PCR).
    Results. Our analysis revealed 43 miRNAs with altered expression profiles in DLBCL compared to EMZL. Seven of the miRNAs down-regulated in DLBCL relative to EMZL showed enrichment for a direct transcriptional repression by the oncoprotein MYC. We also report a possible loss-of-regulation of NFKB1 and its downstream miRNAs. In addition, our analysis identified a group of DLBCLs whose expression profiles resembled that of EMZL. Although transformation of EMZL to DLBCL in the ocular adnexal region is rare, we hypothesize that the intermediate group potentially may derive from transformation of EMZL that was not recognized by histology.
    Conclusions. We conclude that fundamental differences in miRNA expression exist between ocular adnexal EMZL and DLBCL, mainly due to differences in MYC and NF-ĸB regulatory pathways

    Original languageEnglish
    JournalInvestigative Ophthalmology & Visual Science
    Volume54
    Issue number8
    Pages (from-to)5169-5175
    ISSN0146-0404
    DOIs
    Publication statusPublished - 2013

    Keywords

    • Adult
    • Aged
    • Aged, 80 and over
    • Conjunctival Neoplasms
    • Eye Neoplasms
    • Female
    • Follow-Up Studies
    • Gene Expression Regulation, Neoplastic
    • Humans
    • Lacrimal Apparatus
    • Lymphoma, Large B-Cell, Diffuse
    • Male
    • MicroRNAs
    • Middle Aged
    • NF-kappa B p50 Subunit
    • Orbital Neoplasms
    • Protein Array Analysis
    • Proto-Oncogene Proteins c-myc
    • RNA, Neoplasm
    • Real-Time Polymerase Chain Reaction
    • MYC protein, human
    • NFKB1 protein, human

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