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Initial genome sequencing and analysis of multiple myeloma

Author

Listed:
  • Michael A. Chapman

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center
    Present address: Department of Haematology, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ, UK.)

  • Michael S. Lawrence

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center)

  • Jonathan J. Keats

    (Mayo Clinic Arizona, 13400 East Shea Boulevard
    The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor)

  • 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
    The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor)

  • Mazhar Adli

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center
    Massachusetts General Hospital, 55 Fruit Street)

  • Kenneth C. Anderson

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    Dana-Farber Cancer Institute, 44 Binney Street)

  • 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
    Multiple Myeloma Research Foundation, 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
    The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor)

  • Bradley E. Bernstein

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center
    Massachusetts General Hospital, 55 Fruit Street
    Harvard Medical School
    Howard Hughes Medical Institute)

  • Yotam Drier

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center
    Weizmann Institute of Science)

  • Rafael Fonseca

    (Mayo Clinic Arizona, 13400 East Shea Boulevard
    The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor)

  • 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
    The Ohio State University Medical Center, 320 West 10th Avenue)

  • Sundar Jagannath

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    St Vincent’s Comprehensive Cancer Center, 325 West 15th Street)

  • Andrzej J. Jakubowiak

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive)

  • Amrita Krishnan

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    City of Hope Comprehensive Cancer Center, 1500 East Duarte Road)

  • Joan Levy

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    Multiple Myeloma Research Foundation, 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
    Winship Cancer Institute, Emory University, 1365-C Clifton Road)

  • Scott Mahan

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center)

  • Bunmi Mfuko

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    Multiple Myeloma Research Foundation, 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
    Multiple Myeloma Research Foundation, 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
    Mayo Clinic Rochester)

  • 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
    John Theurer Cancer Center at Hackensack University Medical Center, 92 Second Street)

  • Andrey Sivachenko

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center)

  • A. Keith Stewart

    (Mayo Clinic Arizona, 13400 East Shea Boulevard
    The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor)

  • Suzanne Trudel

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    Princess Margaret Hospital, 610 University Avenue)

  • Ravi Vij

    (The Multiple Myeloma Research Consortium, 383 Main Avenue, 5th Floor
    Washington University School of Medicine, Washington University in St Louis)

  • 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
    University of Chicago Medical Center, 5841 South Maryland Avenue)

  • 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
    Dana-Farber Cancer Institute, 44 Binney Street
    Harvard Medical School)

  • Levi A. Garraway

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center
    Dana-Farber Cancer Institute, 44 Binney Street)

  • Matthew Meyerson

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center
    Dana-Farber Cancer Institute, 44 Binney Street
    Harvard Medical School)

  • Eric S. Lander

    (The Eli and Edythe L. Broad Institute, 7 Cambridge Center
    Harvard Medical School
    Massachusetts Institute of Technology)

  • 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
    Dana-Farber Cancer Institute, 44 Binney Street
    Harvard Medical School
    Howard Hughes Medical Institute)

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.

Suggested Citation

  • 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 & , 2011. "Initial genome sequencing and analysis of multiple myeloma," Nature, Nature, vol. 471(7339), pages 467-472, March.
    • Handle: RePEc:nat:nature:v:471:y:2011:i:7339:d:10.1038_nature09837
    DOI: 10.1038/nature09837
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    Citations

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    Cited by:

    1. Danielle C. Croucher & Laura M. Richards & Serges P. Tsofack & Daniel Waller & Zhihua Li & Ellen Nong Wei & Xian Fang Huang & Marta Chesi & P. Leif Bergsagel & Michael Sebag & Trevor J. Pugh & Suzanne, 2021. "Longitudinal single-cell analysis of a myeloma mouse model identifies subclonal molecular programs associated with progression," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Yang Ni & Veerabhadran Baladandayuthapani & Marina Vannucci & Francesco C. Stingo, 2022. "Bayesian graphical models for modern biological applications," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 31(2), pages 197-225, June.
    3. Luigi Augugliaro & Veronica Vinciotti & Ernst C. Wit, 2022. "Extending graphical models for applications: on covariates, missingness and normality," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 31(2), pages 241-251, June.
    4. Yandan Yang & Arnold Bolomsky & Thomas Oellerich & Ping Chen & Michele Ceribelli & Björn Häupl & George W. Wright & James D. Phelan & Da Wei Huang & James W. Lord & Callie K. Winkle & Xin Yu & Jan Wis, 2022. "Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Mark Bustoros & Shankara Anand & Romanos Sklavenitis-Pistofidis & Robert Redd & Eileen M. Boyle & Benny Zhitomirsky & Andrew J. Dunford & Yu-Tzu Tai & Selina J. Chavda & Cody Boehner & Carl Jannes Neu, 2022. "Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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