Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma

Frances E. Lock, Rita Rebollo, Katharine Miceli-Royer, Liane Gagnier, Sabrina Kuah, Artem Babaian, Maialen Sistiaga-Poveda, C. Benjamin Lai, Oksana Nemirovsky, Isabel Serrano, Christian Steidl, Mohammad M. Karimi, Dixie L. Mager

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences harbor multiple regulatory motifs and hence are capable of influencing expression of host genes. In response to environmental changes, TEs are known to be released from epigenetic repression and to become transcriptionally active. Such activation could also lead to lineage-inappropriate activation of oncogenes, as one study described in Hodgkin lymphoma. However, little further evidence for this mechanism in other cancers has been reported. Here, we reanalyzed whole transcriptome data from a large cohort of patients with diffuse large B-cell lymphoma (DLBCL) compared with normal B-cell centroblasts to detect genes ectopically expressed through activation of TE promoters. We have identified 98 such TE-gene chimeric transcripts that were exclusively expressed in primary DLBCL cases and confirmed several in DLBCL-derived cell lines. We further characterized a TEgene chimeric transcript involving a fatty acid-binding protein gene (LTR2-FABP7), normally expressed in brain, that was ectopically expressed in a subset of DLBCL patients through the use of an endogenous retroviral LTR promoter of the LTR2 family. The LTR2-FABP7 chimeric transcript encodes a novel chimeric isoform of the protein with characteristics distinct from native FABP7. In vitro studies reveal a dependency for DLBCL cell line proliferation and growth on LTR2-FABP7 chimeric protein expression. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in cancer and suggest that LTR2-FABP7 may contribute to the pathogenesis of DLBCL in a subgroup of patients. gene regulation, endogenous retroviruses, alternative promoters.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number34
DOIs
Publication statusPublished - 26 Aug 2014
Externally publishedYes

Fingerprint

Retroelements
Lymphoma, Large B-Cell, Diffuse
DNA Transposable Elements
Protein Isoforms
Genes
Epigenetic Repression
Endogenous Retroviruses
Gene Expression
Cell Line
Fatty Acid-Binding Proteins
Regulator Genes
Hodgkin Disease
Oncogenes
Transcriptome
Neoplasms
B-Lymphocytes
Cell Proliferation
Genome
Brain
Growth

Keywords

  • Alternative promoters
  • Endogenous retroviruses
  • Gene regulation

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma. / Lock, Frances E.; Rebollo, Rita; Miceli-Royer, Katharine; Gagnier, Liane; Kuah, Sabrina; Babaian, Artem; Sistiaga-Poveda, Maialen; Lai, C. Benjamin; Nemirovsky, Oksana; Serrano, Isabel; Steidl, Christian; Karimi, Mohammad M.; Mager, Dixie L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 34, 26.08.2014.

Research output: Contribution to journalArticle

Lock, FE, Rebollo, R, Miceli-Royer, K, Gagnier, L, Kuah, S, Babaian, A, Sistiaga-Poveda, M, Lai, CB, Nemirovsky, O, Serrano, I, Steidl, C, Karimi, MM & Mager, DL 2014, 'Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 34. https://doi.org/10.1073/pnas.1405507111
Lock, Frances E. ; Rebollo, Rita ; Miceli-Royer, Katharine ; Gagnier, Liane ; Kuah, Sabrina ; Babaian, Artem ; Sistiaga-Poveda, Maialen ; Lai, C. Benjamin ; Nemirovsky, Oksana ; Serrano, Isabel ; Steidl, Christian ; Karimi, Mohammad M. ; Mager, Dixie L. / Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 34.
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