IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v471y2011i7339d10.1038_nature09837.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature09837
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature09837?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. Sinan Xiong & Jianbiao Zhou & Tze King Tan & Tae-Hoon Chung & Tuan Zea Tan & Sabrina Hui-Min Toh & Nicole Xin Ning Tang & Yunlu Jia & Yi Xiang See & Melissa Jane Fullwood & Takaomi Sanda & Wee-Joo Chn, 2024. "Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. 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.
    5. 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.
    6. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:471:y:2011:i:7339:d:10.1038_nature09837. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.