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Long Non-Coding RNAs as Molecular Signatures for Canine B-Cell Lymphoma Characterization

Institute of Oncology Research, Universita’ della Svizzera Italiana, 6500 Bellinzona, Switzerland
Swiss Institute of Bioinformatics, 1000 Lausanne, Switzerland
Department of Computer Science, University of Verona, 37100 Verona, Italy
Department of Comparative Biomedicine and Food Science, University of Padova, 35100 Padova, Italy
Centro Oncologico Veterinario, 40037 Sasso Marconi BO, Italy
Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors share senior authorship.
Non-Coding RNA 2019, 5(3), 47;
Received: 1 August 2019 / Revised: 6 September 2019 / Accepted: 16 September 2019 / Published: 19 September 2019
(This article belongs to the Special Issue Non-Coding RNAs: Variations and Disease)
Background: Diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) are the most common B-cell lymphomas (BCL) in dogs. Recent investigations have demonstrated overlaps of these histotypes with the human counterparts, including clinical presentation, biologic behavior, tumor genetics, and treatment response. The molecular mechanisms that underlie canine BCL are still unknown and new studies to improve diagnosis, therapy, and the utilization of canine species as spontaneous animal tumor models are undeniably needed. Recent work using human DLBCL transcriptomes has suggested that long non-coding RNAs (lncRNAs) play a key role in lymphoma pathogenesis and pinpointed a restricted number of lncRNAs as potential targets for further studies. Results: To expand the knowledge of non-coding molecules involved in canine BCL, we used transcriptomes obtained from a cohort of 62 dogs with newly-diagnosed multicentric DLBCL, MZL and FL that had undergone complete staging work-up and were treated with chemotherapy or chemo-immunotherapy. We developed a customized R pipeline performing a transcriptome assembly by multiple algorithms to uncover novel lncRNAs, and delineate genome-wide expression of unannotated and annotated lncRNAs. Our pipeline also included a new package for high performance system biology analysis, which detects high-scoring network biological neighborhoods to identify functional modules. Moreover, our customized pipeline quantified the expression of novel and annotated lncRNAs, allowing us to subtype DLBCLs into two main groups. The DLBCL subtypes showed statistically different survivals, indicating the potential use of lncRNAs as prognostic biomarkers in future studies. Conclusions: In this manuscript, we describe the methodology used to identify lncRNAs that differentiate B-cell lymphoma subtypes and we interpreted the biological and clinical values of the results. We inferred the potential functions of lncRNAs to obtain a comprehensive and integrative insight that highlights their impact in this neoplasm. View Full-Text
Keywords: long non-coding RNA; analysis pipeline; lymphoma; prognostic signature long non-coding RNA; analysis pipeline; lymphoma; prognostic signature
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Cascione, L.; Giudice, L.; Ferraresso, S.; Marconato, L.; Giannuzzi, D.; Napoli, S.; Bertoni, F.; Giugno, R.; Aresu, L. Long Non-Coding RNAs as Molecular Signatures for Canine B-Cell Lymphoma Characterization. Non-Coding RNA 2019, 5, 47.

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