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Life histories of myeloproliferative neoplasms inferred from phylogenies

Author

Listed:
  • Nicholas Williams

    (Wellcome Genome Campus)

  • Joe Lee

    (Wellcome Genome Campus
    Jeffrey Cheah Biomedical Centre)

  • Emily Mitchell

    (Wellcome Genome Campus
    Jeffrey Cheah Biomedical Centre
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Luiza Moore

    (Wellcome Genome Campus)

  • E. Joanna Baxter

    (University of Cambridge)

  • James Hewinson

    (Wellcome Genome Campus)

  • Kevin J. Dawson

    (Wellcome Genome Campus)

  • Andrew Menzies

    (Wellcome Genome Campus)

  • Anna L. Godfrey

    (Cambridge University Hospitals NHS Foundation Trust)

  • Anthony R. Green

    (Jeffrey Cheah Biomedical Centre
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Peter J. Campbell

    (Wellcome Genome Campus
    Jeffrey Cheah Biomedical Centre
    University of Cambridge)

  • Jyoti Nangalia

    (Wellcome Genome Campus
    Jeffrey Cheah Biomedical Centre
    University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

Abstract

Mutations in cancer-associated genes drive tumour outgrowth, but our knowledge of the timing of driver mutations and subsequent clonal dynamics is limited1–3. Here, using whole-genome sequencing of 1,013 clonal haematopoietic colonies from 12 patients with myeloproliferative neoplasms, we identified 580,133 somatic mutations to reconstruct haematopoietic phylogenies and determine clonal histories. Driver mutations were estimated to occur early in life, including the in utero period. JAK2V617F was estimated to have been acquired by 33 weeks of gestation to 10.8 years of age in 5 patients in whom JAK2V617F was the first event. DNMT3A mutations were acquired by 8 weeks of gestation to 7.6 years of age in 4 patients, and a PPM1D mutation was acquired by 5.8 years of age. Additional genomic events occurred before or following JAK2V617F acquisition and as independent clonal expansions. Sequential driver mutation acquisition was separated by decades across life, often outcompeting ancestral clones. The mean latency between JAK2V617F acquisition and diagnosis was 30 years (range 11–54 years). Estimated historical rates of clonal expansion varied substantially (3% to 190% per year), increased with additional driver mutations, and predicted latency to diagnosis. Our study suggests that early driver mutation acquisition and life-long growth and evolution underlie adult myeloproliferative neoplasms, raising opportunities for earlier intervention and a new model for cancer development.

Suggested Citation

  • Nicholas Williams & Joe Lee & Emily Mitchell & Luiza Moore & E. Joanna Baxter & James Hewinson & Kevin J. Dawson & Andrew Menzies & Anna L. Godfrey & Anthony R. Green & Peter J. Campbell & Jyoti Nanga, 2022. "Life histories of myeloproliferative neoplasms inferred from phylogenies," Nature, Nature, vol. 602(7895), pages 162-168, February.
  • Handle: RePEc:nat:nature:v:602:y:2022:i:7895:d:10.1038_s41586-021-04312-6
    DOI: 10.1038/s41586-021-04312-6
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    Cited by:

    1. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis," IJERPH, MDPI, vol. 19(24), pages 1-57, December.
    2. Mohammed Ferdous-Ur Rahman & Yue Yang & Bao T. Le & Avik Dutta & Julia Posyniak & Patrick Faughnan & Mohammad A. Sayem & Nadine S. Aguilera & Golam Mohi, 2022. "Interleukin-1 contributes to clonal expansion and progression of bone marrow fibrosis in JAK2V617F-induced myeloproliferative neoplasm," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Giulia Schiroli & Vinay Kartha & Fabiana M. Duarte & Trine A. Kristiansen & Christina Mayerhofer & Rojesh Shrestha & Andrew Earl & Yan Hu & Tristan Tay & Catherine Rhee & Jason D. Buenrostro & David T, 2024. "Cell of origin epigenetic priming determines susceptibility to Tet2 mutation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Yash Pershad & Taralynn Mack & Hannah Poisner & Yasminka A. Jakubek & Adrienne M. Stilp & Braxton D. Mitchell & Joshua P. Lewis & Eric Boerwinkle & Ruth J. F. Loos & Nathalie Chami & Zhe Wang & Kathle, 2024. "Determinants of mosaic chromosomal alteration fitness," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    5. Diletta Fontana & Ilaria Crespiatico & Valentina Crippa & Federica Malighetti & Matteo Villa & Fabrizio Angaroni & Luca De Sano & Andrea Aroldi & Marco Antoniotti & Giulio Caravagna & Rocco Piazza & A, 2023. "Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Derek W. Brown & Liam D. Cato & Yajie Zhao & Satish K. Nandakumar & Erik L. Bao & Eugene J. Gardner & Aubrey K. Hubbard & Alexander DePaulis & Thomas Rehling & Lei Song & Kai Yu & Stephen J. Chanock &, 2023. "Shared and distinct genetic etiologies for different types of clonal hematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Heather E. Machado & Nina F. Øbro & Nicholas Williams & Shengjiang Tan & Ahmed Z. Boukerrou & Megan Davies & Miriam Belmonte & Emily Mitchell & E. Joanna Baxter & Nicole Mende & Anna Clay & Philip Anc, 2023. "Convergent somatic evolution commences in utero in a germline ribosomopathy," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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