Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma

Author:

Walker Brian A.1ORCID,Mavrommatis Konstantinos2,Wardell Christopher P.1ORCID,Ashby T. Cody1,Bauer Michael1,Davies Faith E.1,Rosenthal Adam3,Wang Hongwei3,Qu Pingping3,Hoering Antje3,Samur Mehmet4,Towfic Fadi5,Ortiz Maria6,Flynt Erin5,Yu Zhinuan5,Yang Zhihong5,Rozelle Dan7,Obenauer John7,Trotter Matthew6,Auclair Daniel8,Keats Jonathan9,Bolli Niccolo10,Fulciniti Mariateresa4,Szalat Raphael4,Moreau Philippe11,Durie Brian12,Stewart A. Keith13,Goldschmidt Hartmut14,Raab Marc S.1415,Einsele Hermann16,Sonneveld Pieter17,San Miguel Jesus18,Lonial Sagar19,Jackson Graham H.20,Anderson Kenneth C.4,Avet-Loiseau Herve2122,Munshi Nikhil4,Thakurta Anjan5,Morgan Gareth J.1

Affiliation:

1. Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR;

2. Celgene Corporation, San Francisco, CA;

3. Cancer Research and Biostatistics, Seattle, WA;

4. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;

5. Celgene Corporation, Summit, NJ;

6. Celgene Institute of Translational Research Europe, Sevilla, Spain;

7. Rancho BioSciences, San Diego, CA;

8. Multiple Myeloma Research Foundation, Norwalk, CT;

9. Translational Genomics Research Institute, Phoenix, AZ;

10. Department of Oncology, University of Milan, Milan, Italy;

11. Department of Hematology, University of Nantes, Nantes, France;

12. Cedars-Sinai Samuel Oschin Cancer Center, Los Angeles, CA;

13. Department of Hematology, Mayo Clinic, Scottsdale, AZ;

14. Department of Medicine V, Hematology and Oncology, University Hospital of Heidelberg, Heidelberg, Germany;

15. German Cancer Research Center, Heidelberg, Germany;

16. Department of Internal Medicine II, Wurzburg University, Wurzburg, Germany;

17. Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands;

18. Centro Investigacion Medica Aplicada, Clinica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, Centro de Investigación Biomédica en Red de Oncología, Pamplona, Spain;

19. Winship Cancer Institute, Emory University, Atlanta, GA;

20. Department of Haematology, Newcastle University, Newcastle, United Kingdom;

21. Centre de Recherche en Cancérologie de Toulouse Institut National de la Santé et de la Recherche Médicale U1037, Toulouse, France; and

22. L’Institut Universitaire du Cancer de Toulouse Oncopole, Centre Hospitalier Universitaire, Toulouse, France

Abstract

Key Points Using the largest set of patients with newly diagnosed myeloma, we identified 63 mutated driver genes. We identified oncogenic dependencies, particularly relating to primary translocations, indicating a nonrandom accumulation of genetic hits.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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