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

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