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

• DOI: 10.1073/pnas.1405507111
• Publication Date: 2014-08-12T02:59:19Z
• Authors: Frances E. Lock; Rita Rebollo; Katharine Miceli-...; Liane Gagnier; Sabrina Kuah; Artem Babaian; Maialen Sistiaga-...; C. Benjamin Lai; Oksana Nemirovsky; Isabel Serrano; Christian Steidl; Mohammad M. Karimi; Dixie L. Mager
• Keywords: Transcriptional Activation; 570; [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]; Oncogene Proteins, Fusion; Retroelements; 610; endogenous retroviruses; Epigenesis, Genetic; Cell Line, Tumor; Humans; Protein Isoforms; Genetic Testing; RNA, Messenger; RNA, Neoplasm; alternative promoters; Promoter Regions, Genetic; Tumor Suppressor Proteins; Fatty Acids; Terminal Repeat Sequences; 3. Good health; Gene Expression Regulation, Neoplastic; Tissue Array Analysis; DNA Transposable Elements; Lymphoma, Large B-Cell, Diffuse; gene regulation; Carrier Proteins; Fatty Acid-Binding Protein 7

Significance

Sequences derived from transposable elements (TEs) are abundant in the human genome and can influence gene expression. In normal cells, most TEs are silenced by epigenetic mechanisms such as DNA methylation but, in cancer, normally dormant TEs can become active. We hypothesized that cancer-specific release of epigenetic suppression of TEs could result in gene expression perturbations, which could promote oncogenesis. Using a bioinformatics method, we identified many genes expressed in diffuse large B-cell lymphoma (DLBCL) via activation of TE promoters. Further analysis of one, FABP7 , showed it was expressed in some DLBCL samples through use of a TE promoter. The TE-driven FABP7 transcript encodes a novel isoform of the protein, which is required for optimal DLBCL cell line proliferation.