TY - JOUR
T1 - MicroRNA profiling in ocular adnexal lymphoma
T2 - a role for MYC and NFKB1 mediated dysregulation of microRNA expression in aggressive disease
AU - Hother, Christoffer
AU - Rasmussen, Peter Kristian
AU - Joshi, Tejal
AU - Reker, Ditte
AU - Ralfkiær, Ulrik
AU - Workman, Christopher T
AU - Heegaard, Steffen
AU - Ralfkiær, Elisabeth
AU - Grønbæk, Kirsten
PY - 2013/8
Y1 - 2013/8
N2 - 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-+B regulatory pathways.
AB - 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-+B regulatory pathways.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Conjunctival Neoplasms
KW - Eye Neoplasms
KW - Female
KW - Follow-Up Studies
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Lacrimal Apparatus
KW - Lymphoma, Large B-Cell, Diffuse
KW - Male
KW - MicroRNAs
KW - Middle Aged
KW - NF-kappa B p50 Subunit
KW - Orbital Neoplasms
KW - Protein Array Analysis
KW - Proto-Oncogene Proteins c-myc
KW - RNA, Neoplasm
KW - Real-Time Polymerase Chain Reaction
U2 - 10.1167/iovs.13-12272
DO - 10.1167/iovs.13-12272
M3 - Journal article
C2 - 23821202
SN - 0146-0404
VL - 54
SP - 5169
EP - 5175
JO - Investigative Ophthalmology & Visual Science
JF - Investigative Ophthalmology & Visual Science
IS - 8
ER -