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; 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; Todd R Golub

doi:10.1038/nature09837

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Initial genome sequencing and analysis of multiple myeloma

Journal article

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Peer reviewed

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, …

Nature (London), Vol.471(7339), pp.467-472

03/24/2011

DOI: https://doi.org/10.1038/nature09837

PMCID: PMC3560292

PMID: 21430775

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 tumor genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the dataset. 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 signaling was suggested 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.

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Title: Initial genome sequencing and analysis of multiple myeloma
Creators: Michael A Chapman - Washington University in St. Louis
Michael S Lawrence - Washington University in St. Louis
Jonathan J Keats - Washington University in St. Louis
Kristian Cibulskis - Washington University in St. Louis
Carrie Sougnez - Washington University in St. Louis
Anna C Schinzel - Washington University in St. Louis
Christina L Harview - Washington University in St. Louis
Jean-Philippe Brunet - Washington University in St. Louis
Gregory J Ahmann - Washington University in St. Louis
Mazhar Adli - Washington University in St. Louis
Kenneth C Anderson - Washington University in St. Louis
Kristin G Ardlie - Washington University in St. Louis
Daniel Auclair - Washington University in St. Louis
Angela Baker - Washington University in St. Louis
P. Leif Bergsagel - Washington University in St. Louis
Bradley E Bernstein - Washington University in St. Louis
Yotam Drier - Washington University in St. Louis
Rafael Fonseca - Washington University in St. Louis
Stacey B Gabriel - Washington University in St. Louis
Craig C Hofmeister - Washington University in St. Louis
Sundar Jagannath - Washington University in St. Louis
Andrzej J Jakubowiak - Washington University in St. Louis
Amrita Krishnan - Washington University in St. Louis
Joan Levy - Washington University in St. Louis
Ted Liefeld - Washington University in St. Louis
Sagar Lonial - Washington University in St. Louis
Scott Mahan - Washington University in St. Louis
Bunmi Mfuko - Washington University in St. Louis
Stefano Monti - Washington University in St. Louis
Louise M Perkins - Washington University in St. Louis
Robb Onofrio - Washington University in St. Louis
Trevor J Pugh - Washington University in St. Louis
S Vincent Rajkumar - Washington University in St. Louis
Alex H Ramos - Washington University in St. Louis
David S Siegel - Washington University in St. Louis
Andrey Sivachenko - Washington University in St. Louis
Suzanne Trudel - Washington University in St. Louis
Ravi Vij - Washington University in St. Louis
Douglas Voet - Washington University in St. Louis
Wendy Winckler - Washington University in St. Louis
Todd Zimmerman - Washington University in St. Louis
John Carpten - Washington University in St. Louis
Jeff Trent - Washington University in St. Louis
William C Hahn - Washington University in St. Louis
Levi A Garraway - Washington University in St. Louis
Matthew Meyerson - Washington University in St. Louis
Eric S Lander - Washington University in St. Louis
Gad Getz - Washington University in St. Louis
Todd R Golub - Washington University in St. Louis
Publication Details: Nature (London), Vol.471(7339), pp.467-472
Identifiers: 9924086544701921
Academic Unit: Rabb School of Continuing Studies, Division of Graduate Professional Studies
Language: English
Resource Type: Journal article

Initial genome sequencing and analysis of multiple myeloma

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