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Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma

  1. Author:
    Hua, Xing
    Zhao, Wei
    Pesatori, Angela C.
    Consonni, Dario
    Caporaso, Neil E.
    Zhang, Tongwu
    Zhu, Bin
    Wang,Mingyi
    Jones,Kristine
    Hicks,Belynda
    Song,Lei
    Sampson, Joshua
    Wedge, David C.
    Shi, Jianxin
    Landi, Maria Teresa

  2. Author Address

    NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.NCI, Integrat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.Fdn IRCCS Ca Granda Osped Maggiore Policlin, Occupat Hlth Unit, Milan, Italy.NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.Leidos Biomed Res Inc, Canc Genome Res Lab, Bethesda, MD USA.Big Data Inst, Old Rd Campus, Oxford, England.Oxford NIHR Biomed Res Ctr, Oxford, England.
    1. Year: 2020
    2. Date: MAY 18
  2. Journal: NATURE COMMUNICATIONS
  3. NATURE PUBLISHING GROUP,
    1. 11
    2. 1
  5. Type of Article: Article
  6. ISSN: 2041-1723
  1. Abstract:

    Intratumor heterogeneity (ITH) of genomic alterations may impact prognosis of lung adenocarcinoma (LUAD). Here, we investigate ITH of somatic copy number alterations (SCNAs), DNA methylation, and point mutations in lung cancer driver genes in 292 tumor samples from 84 patients with LUAD. LUAD samples show substantial SCNA and methylation ITH, and clonal architecture analyses present congruent evolutionary trajectories for SCNAs and DNA methylation aberrations. Methylation ITH mapping to gene promoter areas or tumor suppressor genes is low. Moreover, ITH composed of genetic and epigenetic mechanisms altering the same cancer driver genes is shown in several tumors. To quantify ITH for valid statistical association analyses, we develope an average pairwise ITH index (APITH), which does not depend on the number of samples per tumor. Both APITH indexes for SCNAs and methylation aberrations show significant associations with poor prognosis. This study further establishes the important clinical implications of genetic and epigenetic ITH in LUAD. Many tumors are known to be heterogeneous. Here, the authors examined multiple samples from 84 patients with lung adenocarcinoma and demonstrate that the intratumor heterogeneity of methylation and copy number associates with poor prognosis.

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External Sources

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  2. DOI: 10.1038/s41467-020-16295-5
  3. View record in Web of Science®
  4. WOS: 000536698500002

Library Notes

  1. Fiscal Year: FY2019-2020
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