Expressed fusion gene landscape and its impact in multiple myeloma.
Fiche publication
Date publication
décembre 2017
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHRETIEN Marie-Lorraine
Tous les auteurs :
Cleynen A, Szalat R, Kemal Samur M, Robiou du Pont S, Buisson L, Boyle E, Chretien ML, Anderson K, Minvielle S, Moreau P, Attal M, Parmigiani G, Corre J, Munshi N, Avet-Loiseau H
Lien Pubmed
Résumé
Multiple myeloma is a plasma cell malignancy characterized by recurrent IgH translocations and well described genomic heterogeneity. Although transcriptome profiles in multiple myeloma has been described, landscape of expressed fusion genes and their clinical impact remains unknown. To provide a comprehensive and detailed fusion gene cartography and suggest new mechanisms of tumorigenesis in multiple myeloma, we performed RNA sequencing in a cohort of 255 newly diagnosed and homogeneously treated multiple myeloma patients with long follow-up. Here, we report that patients have on average 5.5 expressed fusion genes. Kappa and lambda light chains and IgH genes are main partners in a third of all fusion genes. We also identify recurrent fusion genes that significantly impact both progression-free and overall survival and may act as drivers of the disease. Lastly, we find a correlation between the number of fusions, the age of patients and the clinical outcome, strongly suggesting that genomic instability drives prognosis of the disease.
Mots clés
Aged, Female, Gene Fusion, Humans, Immunoglobulin Heavy Chains, genetics, Immunoglobulin kappa-Chains, genetics, Immunoglobulin lambda-Chains, genetics, Male, Middle Aged, Multiple Myeloma, genetics, Sequence Analysis, RNA, Translocation, Genetic
Référence
Nat Commun. 2017 12 1;8(1):1893