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Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma

Author

Listed:
  • Xing Hua

    (DHHS)

  • Wei Zhao

    (DHHS)

  • Angela C. Pesatori

    (University of Milan
    Occupational Health Unit)

  • Dario Consonni

    (Occupational Health Unit)

  • Neil E. Caporaso

    (National Cancer Institute, NIH, DHHS)

  • Tongwu Zhang

    (DHHS)

  • Bin Zhu

    (DHHS)

  • Mingyi Wang

    (Leidos Biomedical Research Inc.)

  • Kristine Jones

    (Leidos Biomedical Research Inc.)

  • Belynda Hicks

    (Leidos Biomedical Research Inc.)

  • Lei Song

    (Leidos Biomedical Research Inc.)

  • Joshua Sampson

    (DHHS)

  • David C. Wedge

    (Big Data Institute
    Oxford NIHR Biomedical Research Centre)

  • Jianxin Shi

    (DHHS)

  • Maria Teresa Landi

    (DHHS)

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.

Suggested Citation

  • Xing Hua & Wei Zhao & Angela C. Pesatori & Dario Consonni & Neil E. Caporaso & Tongwu Zhang & Bin Zhu & Mingyi Wang & Kristine Jones & Belynda Hicks & Lei Song & Joshua Sampson & David C. Wedge & Jian, 2020. "Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16295-5
    DOI: 10.1038/s41467-020-16295-5
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    Cited by:

    1. Sijia Cui & Nicholas McGranahan & Jing Gao & Peng Chen & Wei Jiang & Lingrong Yang & Li Ma & Junfang Liao & Tian Xie & Congying Xie & Tariq Enver & Shixiu Wu, 2023. "Tracking the evolution of esophageal squamous cell carcinoma under dynamic immune selection by multi-omics sequencing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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