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. 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.
    5. 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.
    6. 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.
    7. 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.
    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. 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.
    2. 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.
    3. 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.
    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. Feifei Xie & Shuzhen Luo & Dongbing Liu & Xiaojing Lu & Ming Wang & Xiaoxiao Liu & Fujian Jia & Yuzhi Pang & Yanying Shen & Chunling Zeng & Xinli Ma & Daoqiang Tang & Lin Tu & Linxi Yang & Yumei Cheng, 2024. "Genomic and transcriptomic landscape of human gastrointestinal stromal tumors," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    7. 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.
    8. Guozhong Jiang & Zhizhong Wang & Zhenguo Cheng & Weiwei Wang & Shuangshuang Lu & Zifang Zhang & Chinedu A. Anene & Faraz Khan & Yue Chen & Emma Bailey & Huisha Xu & Yunshu Dong & Peinan Chen & Zhongxi, 2024. "The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Marjan M. Naeini & Felicity Newell & Lauren G. Aoude & Vanessa F. Bonazzi & Kalpana Patel & Guy Lampe & Lambros T. Koufariotis & Vanessa Lakis & Venkateswar Addala & Olga Kondrashova & Rebecca L. John, 2023. "Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Yasuhiko Haga & Yoshitaka Sakamoto & Keiko Kajiya & Hitomi Kawai & Miho Oka & Noriko Motoi & Masayuki Shirasawa & Masaya Yotsukura & Shun-Ichi Watanabe & Miyuki Arai & Junko Zenkoh & Kouya Shiraishi &, 2023. "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    11. Ambrocio Sanchez & Pedro Ortega & Ramin Sakhtemani & Lavanya Manjunath & Sunwoo Oh & Elodie Bournique & Alexandrea Becker & Kyumin Kim & Cameron Durfee & Nuri Alpay Temiz & Xiaojiang S. Chen & Reuben , 2024. "Mesoscale DNA features impact APOBEC3A and APOBEC3B deaminase activity and shape tumor mutational landscapes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. 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.
    13. Jonathan C. M. Wan & Dennis Stephens & Lingqi Luo & James R. White & Caitlin M. Stewart & Benoît Rousseau & Dana W. Y. Tsui & Luis A. Diaz, 2022. "Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. 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.
    15. Thomas R. W. Oliver & Lia Chappell & Rashesh Sanghvi & Lauren Deighton & Naser Ansari-Pour & Stefan C. Dentro & Matthew D. Young & Tim H. H. Coorens & Hyunchul Jung & Tim Butler & Matthew D. C. Nevill, 2022. "Clonal diversification and histogenesis of malignant germ cell tumours," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    16. 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.
    17. 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.
    18. Ewart Kuijk & Onno Kranenburg & Edwin Cuppen & Arne Van Hoeck, 2022. "Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    19. 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.
    20. Sophie Pénisson & Amaury Lambert & Cristian Tomasetti, 2022. "Evaluating cancer etiology and risk with a mathematical model of tumor evolution," Nature Communications, Nature, vol. 13(1), pages 1-11, 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.