IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-20907-z.html
   My bibliography  Save this article

Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas

Author

Listed:
  • Xin Hu

    (The University of Texas MD Anderson Cancer Center)

  • Marcos R. Estecio

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Runzhe Chen

    (The University of Texas MD Anderson Cancer Center)

  • Alexandre Reuben

    (The University of Texas MD Anderson Cancer Center)

  • Linghua Wang

    (The University of Texas MD Anderson Cancer Center)

  • Junya Fujimoto

    (The University of Texas MD Anderson Cancer Center)

  • Jian Carrot-Zhang

    (Broad Institute of MIT and Harvard
    Dana-Farber Cancer Institute
    Harvard Medical School)

  • Nicholas McGranahan

    (Cancer Research United Kingdom-University College London Lung Cancer Centre of Excellence)

  • Lisha Ying

    (Chinese Academy of Sciences
    Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital))

  • Junya Fukuoka

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Chi-Wan Chow

    (The University of Texas MD Anderson Cancer Center)

  • Hoa H. N. Pham

    (Nagasaki University Graduate School of Biomedical Sciences)

  • Myrna C. B. Godoy

    (The University of Texas MD Anderson Cancer Center)

  • Brett W. Carter

    (The University of Texas MD Anderson Cancer Center)

  • Carmen Behrens

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Jianhua Zhang

    (The University of Texas MD Anderson Cancer Center)

  • Mara B. Antonoff

    (The University of Texas MD Anderson Cancer Center)

  • Boris Sepesi

    (The University of Texas MD Anderson Cancer Center)

  • Yue Lu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Harvey I. Pass

    (New York University Langone Medical Center)

  • Humam Kadara

    (The University of Texas MD Anderson Cancer Center)

  • Paul Scheet

    (The University of Texas MD Anderson Cancer Center)

  • Ara A. Vaporciyan

    (The University of Texas MD Anderson Cancer Center)

  • John V. Heymach

    (The University of Texas MD Anderson Cancer Center)

  • Ignacio I. Wistuba

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • J. Jack Lee

    (The University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (The University of Texas MD Anderson Cancer Center)

  • Dan Su

    (Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital))

  • Jean-Pierre J. Issa

    (Coriell Institute for Medical Research)

  • Jianjun Zhang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8 + T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas.

Suggested Citation

  • Xin Hu & Marcos R. Estecio & Runzhe Chen & Alexandre Reuben & Linghua Wang & Junya Fujimoto & Jian Carrot-Zhang & Nicholas McGranahan & Lisha Ying & Junya Fukuoka & Chi-Wan Chow & Hoa H. N. Pham & Myr, 2021. "Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20907-z
    DOI: 10.1038/s41467-021-20907-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-20907-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-20907-z?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
    ---><---

    Citations

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


    Cited by:

    1. 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.

    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:12:y:2021:i:1:d:10.1038_s41467-021-20907-z. 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.