Initial genome sequencing and analysis of multiple myeloma

Michael A. Chapman, Michael S. Lawrence, Jonathan J. Keats, Kristian Cibulskis, Carrie Sougnez, Anna C. Schinzel, Christina L. Harview, Jean-Philippe Brunet, Gregory J. Ahmann, Mazhar Adli, Kenneth C. Anderson, Kristin G. Ardlie, Daniel Auclair, Angela Baker, P. Leif Bergsagel, Bradley E. Bernstein, Yotam Drier, Rafael Fonseca, Stacey B. Gabriel, Craig C. Hofmeister, Sundar Jagannath, Andrzej J. Jakubowiak, Amrita Krishnan, Joan Levy, Ted Liefeld, Sagar Lonial, Scott Mahan, Bunmi Mfuko, Stefano Monti, Louise M. Perkins, Robb Onofrio, Trevor J. Pugh, S. Vincent Rajkumar, Alex H. Ramos, David S. Siegel, Andrey Sivachenko, A. Keith Stewart, Suzanne Trudel, Ravi Vij, Douglas Voet, Wendy Winckler, Todd Zimmerman, John Carpten, Jeff Trent, William C. Hahn, Levi A. Garraway, Matthew Meyerson, Eric S. Lander, Gad Getz () and Todd R. Golub ()
Additional contact information
Michael A. Chapman: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Michael S. Lawrence: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Jonathan J. Keats: Mayo Clinic Arizona, 13400 East Shea Boulevard
Kristian Cibulskis: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Carrie Sougnez: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Anna C. Schinzel: Dana-Farber Cancer Institute, 44 Binney Street
Christina L. Harview: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Jean-Philippe Brunet: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Gregory J. Ahmann: Mayo Clinic Arizona, 13400 East Shea Boulevard
Mazhar Adli: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Kenneth C. Anderson: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Kristin G. Ardlie: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Daniel Auclair: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Angela Baker: The Translational Genomics Research Institute, 445 North Fifth Street
P. Leif Bergsagel: Mayo Clinic Arizona, 13400 East Shea Boulevard
Bradley E. Bernstein: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Yotam Drier: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Rafael Fonseca: Mayo Clinic Arizona, 13400 East Shea Boulevard
Stacey B. Gabriel: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Craig C. Hofmeister: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Sundar Jagannath: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Andrzej J. Jakubowiak: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Amrita Krishnan: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Joan Levy: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Ted Liefeld: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Sagar Lonial: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Scott Mahan: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Bunmi Mfuko: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Stefano Monti: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Louise M. Perkins: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Robb Onofrio: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Trevor J. Pugh: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
S. Vincent Rajkumar: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Alex H. Ramos: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
David S. Siegel: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Andrey Sivachenko: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
A. Keith Stewart: Mayo Clinic Arizona, 13400 East Shea Boulevard
Suzanne Trudel: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Ravi Vij: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
Douglas Voet: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Wendy Winckler: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Todd Zimmerman: The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
John Carpten: The Translational Genomics Research Institute, 445 North Fifth Street
Jeff Trent: The Translational Genomics Research Institute, 445 North Fifth Street
William C. Hahn: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Levi A. Garraway: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Matthew Meyerson: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Eric S. Lander: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Gad Getz: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Todd R. Golub: The Eli and Edythe L. Broad Institute, 7 Cambridge Center

Nature, 2011, vol. 471, issue 7339, 467-472

Abstract: Abstract Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.

Date: 2011
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DOI: 10.1038/nature09837

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