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, Peter Leif Bergsagel, Bradley E. Bernstein, Yotam Drier, Rafael Fonseca, Stacey B. Gabriel, Craig C. HofmeisterSundar 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, Alexander 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, Todd R. Golub

Research output: Contribution to journalArticle

928 Citations (Scopus)

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-Î °B signalling was indicated by mutations in 11 members of the NF-Î °B 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.

Original languageEnglish (US)
Pages (from-to)467-472
Number of pages6
JournalNature
Volume471
Issue number7339
DOIs
StatePublished - Mar 24 2011

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Multiple Myeloma
Genome
Mutation
Neoplasms
Proto-Oncogene Proteins B-raf
Genes
High-Throughput Nucleotide Sequencing
Protein Biosynthesis
Blood Coagulation
Plasma Cells
Histones
Methylation
Clinical Trials
DNA

ASJC Scopus subject areas

  • General

Cite this

Chapman, M. A., Lawrence, M. S., Keats, J. J., Cibulskis, K., Sougnez, C., Schinzel, A. C., ... Golub, T. R. (2011). Initial genome sequencing and analysis of multiple myeloma. Nature, 471(7339), 467-472. https://doi.org/10.1038/nature09837

Initial genome sequencing and analysis of multiple myeloma. / Chapman, Michael A.; Lawrence, Michael S.; Keats, Jonathan J.; Cibulskis, Kristian; Sougnez, Carrie; Schinzel, Anna C.; Harview, Christina L.; Brunet, Jean Philippe; Ahmann, Gregory J.; Adli, Mazhar; Anderson, Kenneth C.; Ardlie, Kristin G.; Auclair, Daniel; Baker, Angela; Bergsagel, Peter Leif; Bernstein, Bradley E.; Drier, Yotam; Fonseca, Rafael; Gabriel, Stacey B.; Hofmeister, Craig C.; Jagannath, Sundar; Jakubowiak, Andrzej J.; Krishnan, Amrita; Levy, Joan; Liefeld, Ted; Lonial, Sagar; Mahan, Scott; Mfuko, Bunmi; Monti, Stefano; Perkins, Louise M.; Onofrio, Robb; Pugh, Trevor J.; Rajkumar, S Vincent; Ramos, Alex H.; Siegel, David S.; Sivachenko, Andrey; Stewart, Alexander Keith; Trudel, Suzanne; Vij, Ravi; Voet, Douglas; Winckler, Wendy; Zimmerman, Todd; Carpten, John; Trent, Jeff; Hahn, William C.; Garraway, Levi A.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Golub, Todd R.

In: Nature, Vol. 471, No. 7339, 24.03.2011, p. 467-472.

Research output: Contribution to journalArticle

Chapman, MA, Lawrence, MS, Keats, JJ, Cibulskis, K, Sougnez, C, Schinzel, AC, Harview, CL, Brunet, JP, Ahmann, GJ, Adli, M, Anderson, KC, Ardlie, KG, Auclair, D, Baker, A, Bergsagel, PL, Bernstein, BE, Drier, Y, Fonseca, R, Gabriel, SB, Hofmeister, CC, Jagannath, S, Jakubowiak, AJ, Krishnan, A, Levy, J, Liefeld, T, Lonial, S, Mahan, S, Mfuko, B, Monti, S, Perkins, LM, Onofrio, R, Pugh, TJ, Rajkumar, SV, Ramos, AH, Siegel, DS, Sivachenko, A, Stewart, AK, Trudel, S, Vij, R, Voet, D, Winckler, W, Zimmerman, T, Carpten, J, Trent, J, Hahn, WC, Garraway, LA, Meyerson, M, Lander, ES, Getz, G & Golub, TR 2011, 'Initial genome sequencing and analysis of multiple myeloma', Nature, vol. 471, no. 7339, pp. 467-472. https://doi.org/10.1038/nature09837
Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011 Mar 24;471(7339):467-472. https://doi.org/10.1038/nature09837
Chapman, Michael A. ; Lawrence, Michael S. ; Keats, Jonathan J. ; Cibulskis, Kristian ; Sougnez, Carrie ; Schinzel, Anna C. ; Harview, Christina L. ; Brunet, Jean Philippe ; Ahmann, Gregory J. ; Adli, Mazhar ; Anderson, Kenneth C. ; Ardlie, Kristin G. ; Auclair, Daniel ; Baker, Angela ; Bergsagel, Peter Leif ; Bernstein, Bradley E. ; Drier, Yotam ; Fonseca, Rafael ; Gabriel, Stacey B. ; Hofmeister, Craig C. ; Jagannath, Sundar ; Jakubowiak, Andrzej J. ; Krishnan, Amrita ; Levy, Joan ; Liefeld, Ted ; Lonial, Sagar ; Mahan, Scott ; Mfuko, Bunmi ; Monti, Stefano ; Perkins, Louise M. ; Onofrio, Robb ; Pugh, Trevor J. ; Rajkumar, S Vincent ; Ramos, Alex H. ; Siegel, David S. ; Sivachenko, Andrey ; Stewart, Alexander Keith ; Trudel, Suzanne ; Vij, Ravi ; Voet, Douglas ; Winckler, Wendy ; Zimmerman, Todd ; Carpten, John ; Trent, Jeff ; Hahn, William C. ; Garraway, Levi A. ; Meyerson, Matthew ; Lander, Eric S. ; Getz, Gad ; Golub, Todd R. / Initial genome sequencing and analysis of multiple myeloma. In: Nature. 2011 ; Vol. 471, No. 7339. pp. 467-472.
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AU - Hofmeister, Craig C.

AU - Jagannath, Sundar

AU - Jakubowiak, Andrzej J.

AU - Krishnan, Amrita

AU - Levy, Joan

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AU - Mahan, Scott

AU - Mfuko, Bunmi

AU - Monti, Stefano

AU - Perkins, Louise M.

AU - Onofrio, Robb

AU - Pugh, Trevor J.

AU - Rajkumar, S Vincent

AU - Ramos, Alex H.

AU - Siegel, David S.

AU - Sivachenko, Andrey

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AU - Trent, Jeff

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AU - Garraway, Levi A.

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