Long Noncoding RNA Expression Profiling in Normal B-Cell Subsets and Hodgkin Lymphoma Reveals Hodgkin and Reed-Sternberg Cell Specific Long Noncoding RNAs

Mina Masoumeh Tayari, Melanie Winkle, Gertrud Kortman, Jantine Sietzema, Debora de Jong, Martijn Terpstra, Pieter Mestdagh, Frans G. M. Kroese, Lydia Visser, Arjan Diepstra, Klaas Kok, Anke van den Berg, Joost Kluiver*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)


Hodgkin lymphoma (HL) is a malignancy of germinal center (GC) B-cell origin. To explore the role of long noncoding RNAs (lncRNAs) in HL, we studied LncRNA expression patterns in normal B-cell subsets, HL cell lines, and tissues. Naive and memory B cells showed a highly similar lncRNA expression pattern, distinct from GC-B cells. Significant differential expression between I-IL and normal GC-B cells was observed for 475 lncRNA loci. For two validated lncRNAs, an enhanced expression was observed in HL, diffuse large 6-cell lymphoma, and lymphoblastoid cell lines. For a third lncRNA, increased expression levels were observed in HL and part of Burkitt lymphoma cell lines. RNA fluorescence in situ hybridization on primary HL tissues revealed a tumor cell specific expression pattern for all three lncRNAs. A potential cis-regulatory role was observed for 107 differentially expressed lncRNA-mRNA pairs localizing within a 60-kb region. Consistent with a cis-acting role, we showed a preferential nuclear localization for two selected candidates. Thus, we showed dynamic lncRNA expression changes during the transit of normal B cells through the pC reaction and widely deregulated lncRNA expression patterns in HL. Three lncRNAs showed a tumor cell specific expression pattern in HL tissues and might therefore be of value as a biomarker.

Original languageEnglish
Pages (from-to)2462-2472
Number of pages11
JournalThe American Journal of Pathology
Issue number9
Publication statusPublished - Sep-2016


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