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Long intergenic non-coding RNAs have an independent impact on survival in multiple myeloma

Mehmet Kemal Samur 1 Stephane Minvielle 2 Annamaria Gulla 1 Mariateresa Fulciniti 1 Alice Cleynen 3 Anil Samur 1 Raphael Szalat 1 Masood Shammas 1 Florence Magrangeas 2 Yu-Tzu Tai 1 Daniel Auclair 4 Jonathan Keats 5 Paul Richardson 1 Michel Attal 6 Philippe Moreau 2 Kenneth Anderson 1 Giovanni Parmigiani 1 Hervé Avet-Loiseau 6, * Nikhil Munshi 1, 7, *
* Corresponding author
1 Dana-Farber Cancer Institute [Boston, USA]
2 CRCINA-ÉQUIPE 11 - Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
3 UM - Université de Montpellier
4 Multiple Myeloma Research Foundation [Norwalk, CT, USA]
5 TGen - The Translational Genomics Research Institute
6 Pôle IUC - Oncopole - Pôle Institut Universitaire du Cancer - Oncopole [CHU Toulouse]
7 VA Boston Healthcare System
Abstract : Although long intergenic non-coding RNAs (lincRNA) role in various cancers is described, their significance in Multiple Myeloma (MM) remains poorly defined. Here we have studied the lincRNA profile and their clinical impact in MM. We performed RNA-seq on MM cells from 308 newly diagnosed and uniformly treated patients, 16 normal plasma cells and utilized RNA-seq data from 532 newly diagnosed patients from CoMMpass study to analyze for lincRNAs. We observed 869 differentially expressed lincRNAs in MM compared to normal plasma cells. We identified 14 lincRNAs associated with PFS and calculated a risk score to stratify patients. The median PFS between high vs low-risk groups was 17 months vs not-reached (NR); and OS 30 months vs NR, respectively (p < 0.0001 for both). In the independent validation dataset between high and low-risk groups, PFS was 27 vs 42 months (HR 2.06 [1.44−2.96]; p < 0.0005); and 4-year OS 62% vs 86% (HR 2.76 [1.51–5.05]; p < 0.0005) confirming significant clinical relevance of lincRNA in MM. Importantly, lincRNA signature was able to further identify patients with significant differential outcomes within each low and high-risk categories identified using standard risk categorization including cytogenetic/FISH, ISS, and MRD negative or positive. Our results suggest that lincRNAs have an independent effect on MM outcome and provide a rationale to evaluate its molecular and biological impact.
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Submitted on : Friday, June 1, 2018 - 10:46:06 AM
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INSERM | CNRS | UNIV-MONTPELLIER | UNIV-NANTES | CRCINA | UNIV-ANGERS

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Mehmet Kemal Samur, Stephane Minvielle, Annamaria Gulla, Mariateresa Fulciniti, Alice Cleynen, et al.. Long intergenic non-coding RNAs have an independent impact on survival in multiple myeloma. Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2018, Epub ahead of print. ⟨10.1038/s41375-018-0116-y⟩. ⟨inserm-01804867⟩

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