Expressed fusion gene landscape and its impact in multiple myeloma

被引：34
作者：
Cleynen, A. [1 ]
Szalat, R. [2 ]
Samur, M. Kemal [2 ,3 ]
du Pont, S. Robiou [4 ,5 ]
Buisson, L. [4 ,5 ]
Boyle, E. [4 ,5 ]
Chretien, M. L. [6 ]
Anderson, K. [2 ]
Minvielle, S. [7 ]
Moreau, P. [7 ]
Attal, M. [4 ,5 ]
Parmigiani, G. [2 ,3 ]
Corre, J. [4 ,5 ]
Munshi, N. [2 ,8 ]
Avet-Loiseau, H. [4 ,5 ]
机构：
[1] Univ Montpellier, CNRS, Inst Montpellierain Alexander Grothendieck, F-34090 Montpellier, France
[2] Harvard Med Sch, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA
[3] Harvard Med Sch, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA
[4] IUC Oncopole, F-31100 Toulouse, France
[5] INSERM, CRCT, U1037, F-31100 Toulouse, France
[6] CHU Dijon, F-21000 Dijon, France
[7] CHU Nantes, F-44000 Nantes, France
[8] VA Boston Healthcare Syst, West Roxbury, MA 02215 USA
来源：
NATURE COMMUNICATIONS | 2017年 / 8卷
关键词：
MOLECULAR CLASSIFICATION; TRANSCRIPTS; IMMUNOGLOBULIN; TRANSLOCATION; SEQUENCE; MMSET; FGFR3;
D O I：
10.1038/s41467-017-00638-w
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：10
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