IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30694-w.html
   My bibliography  Save this article

Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes

Author

Listed:
  • Mark Bustoros

    (Dana-Farber Cancer Center
    Weill Cornell Medicine)

  • Shankara Anand

    (Broad Institute of MIT & Harvard
    Boston University School of Medicine)

  • Romanos Sklavenitis-Pistofidis

    (Dana-Farber Cancer Center
    Broad Institute of MIT & Harvard)

  • Robert Redd

    (Dana-Farber Cancer Institute)

  • Eileen M. Boyle

    (NYU Langone Health)

  • Benny Zhitomirsky

    (Broad Institute of MIT & Harvard)

  • Andrew J. Dunford

    (Broad Institute of MIT & Harvard)

  • Yu-Tzu Tai

    (Dana-Farber Cancer Center)

  • Selina J. Chavda

    (University College London)

  • Cody Boehner

    (Dana-Farber Cancer Center)

  • Carl Jannes Neuse

    (Dana-Farber Cancer Center
    University of Münster Medical School)

  • Mahshid Rahmat

    (Dana-Farber Cancer Center)

  • Ankit Dutta

    (Dana-Farber Cancer Center)

  • Tineke Casneuf

    (Janssen Research and Development)

  • Raluca Verona

    (Janssen Research and Development)

  • Efstathis Kastritis

    (National and Kapodistrian University of Athens)

  • Lorenzo Trippa

    (Dana-Farber Cancer Institute)

  • Chip Stewart

    (Broad Institute of MIT & Harvard)

  • Brian A. Walker

    (Indiana University)

  • Faith E. Davies

    (NYU Langone Health)

  • Meletios-Athanasios Dimopoulos

    (National and Kapodistrian University of Athens)

  • P. Leif Bergsagel

    (Mayo Clinic)

  • Kwee Yong

    (University College London)

  • Gareth J. Morgan

    (NYU Langone Health)

  • François Aguet

    (Broad Institute of MIT & Harvard)

  • Gad Getz

    (Broad Institute of MIT & Harvard
    Massachusetts General Hospital Cancer Center)

  • Irene M. Ghobrial

    (Dana-Farber Cancer Center
    Broad Institute of MIT & Harvard)

Abstract

Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30694-w
    DOI: 10.1038/s41467-022-30694-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30694-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30694-w?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
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. Brian A. Walker & Christopher P. Wardell & Alex Murison & Eileen M. Boyle & Dil B. Begum & Nasrin M. Dahir & Paula Z. Proszek & Lorenzo Melchor & Charlotte Pawlyn & Martin F. Kaiser & David C. Johnson, 2015. "APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    3. Daniele Ramazzotti & Avantika Lal & Bo Wang & Serafim Batzoglou & Arend Sidow, 2018. "Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    4. Michael S. Lawrence & Petar Stojanov & Craig H. Mermel & James T. Robinson & Levi A. Garraway & Todd R. Golub & Matthew Meyerson & Stacey B. Gabriel & Eric S. Lander & Gad Getz, 2014. "Discovery and saturation analysis of cancer genes across 21 tumour types," Nature, Nature, vol. 505(7484), pages 495-501, January.
    5. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
    6. Francesco Maura & Niccoló Bolli & Nicos Angelopoulos & Kevin J. Dawson & Daniel Leongamornlert & Inigo Martincorena & Thomas J. Mitchell & Anthony Fullam & Santiago Gonzalez & Raphael Szalat & Federic, 2019. "Genomic landscape and chronological reconstruction of driver events in multiple myeloma," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    7. Eileen M. Boyle & Shayu Deshpande & Ruslana Tytarenko & Cody Ashby & Yan Wang & Michael A. Bauer & Sarah K. Johnson & Christopher P. Wardell & Sharmilan Thanendrarajan & Maurizio Zangari & Thierry Fac, 2021. "The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Leo Rasche & Carolina Schinke & Francesco Maura & Michael A. Bauer & Cody Ashby & Shayu Deshpande & Alexandra M. Poos & Maurizio Zangari & Sharmilan Thanendrarajan & Faith E. Davies & Brian A. Walker , 2022. "The spatio-temporal evolution of multiple myeloma from baseline to relapse-refractory states," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Josh N. Vo & Yi-Mi Wu & Jeanmarie Mishler & Sarah Hall & Rahul Mannan & Lisha Wang & Yu Ning & Jin Zhou & Alexander C. Hopkins & James C. Estill & Wallace K. B. Chan & Jennifer Yesil & Xuhong Cao & Ar, 2022. "The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Rotem Katzir & Noam Rudberg & Keren Yizhak, 2022. "Estimating tumor mutational burden from RNA-sequencing without a matched-normal sample," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Atanu Maiti & Adam K. Hedger & Wazo Myint & Vanivilasini Balachandran & Jonathan K. Watts & Celia A. Schiffer & Hiroshi Matsuo, 2022. "Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Sebastian Carrasco Pro & Heather Hook & David Bray & Daniel Berenzy & Devlin Moyer & Meimei Yin & Adam Thomas Labadorf & Ryan Tewhey & Trevor Siggers & Juan Ignacio Fuxman Bass, 2023. "Widespread perturbation of ETS factor binding sites in cancer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Manako Yamaguchi & Hirofumi Nakaoka & Kazuaki Suda & Kosuke Yoshihara & Tatsuya Ishiguro & Nozomi Yachida & Kyota Saito & Haruka Ueda & Kentaro Sugino & Yutaro Mori & Kaoru Yamawaki & Ryo Tamura & Sun, 2022. "Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Qi Zhao & Feng Wang & Yan-Xing Chen & Shifu Chen & Yi-Chen Yao & Zhao-Lei Zeng & Teng-Jia Jiang & Ying-Nan Wang & Chen-Yi Wu & Ying Jing & You-Sheng Huang & Jing Zhang & Zi-Xian Wang & Ming-Ming He & , 2022. "Comprehensive profiling of 1015 patients’ exomes reveals genomic-clinical associations in colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Oriol Pich & Iker Reyes-Salazar & Abel Gonzalez-Perez & Nuria Lopez-Bigas, 2022. "Discovering the drivers of clonal hematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Taichi Igarashi & Marianne Mazevet & Takaaki Yasuhara & Kimiyoshi Yano & Akifumi Mochizuki & Makoto Nishino & Tatsuya Yoshida & Yukihiro Yoshida & Nobuhiko Takamatsu & Akihide Yoshimi & Kouya Shiraish, 2023. "An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    11. Yidong Zhou & Changjun Wang & Hanjiang Zhu & Yan Lin & Bo Pan & Xiaohui Zhang & Xin Huang & Qianqian Xu & Yali Xu & Qiang Sun, 2016. "Diagnostic Accuracy of PIK3CA Mutation Detection by Circulating Free DNA in Breast Cancer: A Meta-Analysis of Diagnostic Test Accuracy," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-15, June.
    12. Sumana Srivatsa & Hesam Montazeri & Gaia Bianco & Mairene Coto-Llerena & Mattia Marinucci & Charlotte K. Y. Ng & Salvatore Piscuoglio & Niko Beerenwinkel, 2022. "Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Benjamin A. Nacev & Francisco Sanchez-Vega & Shaleigh A. Smith & Cristina R. Antonescu & Evan Rosenbaum & Hongyu Shi & Cerise Tang & Nicholas D. Socci & Satshil Rana & Rodrigo Gularte-Mérida & Ahmet Z, 2022. "Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Dillon S. McBride & Sofya K. Garushyants & John Franks & Andrew F. Magee & Steven H. Overend & Devra Huey & Amanda M. Williams & Seth A. Faith & Ahmed Kandeil & Sanja Trifkovic & Lance Miller & Trusha, 2023. "Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    16. Ryan N. Ptashkin & Mark D. Ewalt & Gowtham Jayakumaran & Iwona Kiecka & Anita S. Bowman & JinJuan Yao & Jacklyn Casanova & Yun-Te David Lin & Kseniya Petrova-Drus & Abhinita S. Mohanty & Ruben Bacares, 2023. "Enhanced clinical assessment of hematologic malignancies through routine paired tumor and normal sequencing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    17. Phillips, J.C., 2016. "Autoantibody recognition mechanisms of p53 epitopes," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 451(C), pages 162-170.
    18. Erik Elias & Arman Ardalan & Markus Lindberg & Susanne E. Reinsbach & Andreas Muth & Ola Nilsson & Yvonne Arvidsson & Erik Larsson, 2021. "Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    19. Luan Nguyen & Arne Hoeck & Edwin Cuppen, 2022. "Machine learning-based tissue of origin classification for cancer of unknown primary diagnostics using genome-wide mutation features," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Yoshitaka Sakamoto & Shuhei Miyake & Miho Oka & Akinori Kanai & Yosuke Kawai & Satoi Nagasawa & Yuichi Shiraishi & Katsushi Tokunaga & Takashi Kohno & Masahide Seki & Yutaka Suzuki & Ayako Suzuki, 2022. "Phasing analysis of lung cancer genomes using a long read sequencer," Nature Communications, Nature, vol. 13(1), pages 1-17, 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:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30694-w. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.