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Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA

Author

Listed:
  • Evgeny Izumchenko

    (Johns Hopkins University School of Medicine)

  • Xiaofei Chang

    (Johns Hopkins University School of Medicine)

  • Mariana Brait

    (Johns Hopkins University School of Medicine)

  • Elana Fertig

    (Johns Hopkins University School of Medicine)

  • Luciane T. Kagohara

    (Johns Hopkins University School of Medicine)

  • Atul Bedi

    (Johns Hopkins University School of Medicine)

  • Luigi Marchionni

    (Center for Computational Genomics, Johns Hopkins University School of Medicine)

  • Nishant Agrawal

    (Johns Hopkins University School of Medicine)

  • Rajani Ravi

    (Johns Hopkins University School of Medicine)

  • Sian Jones

    (Personal Genome Diagnostics, Inc.)

  • Mohammad O. Hoque

    (Johns Hopkins University School of Medicine)

  • William H. Westra

    (Johns Hopkins Medical Institutions)

  • David Sidransky

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

Abstract

Lungs resected for adenocarcinomas often harbour minute discrete foci of cytologically atypical pneumocyte proliferations designated as atypical adenomatous hyperplasia (AAH). Evidence suggests that AAH represents an initial step in the progression to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and fully invasive adenocarcinoma. Despite efforts to identify predictive markers of malignant transformation, alterations driving this progression are poorly understood. Here we perform targeted next-generation sequencing on multifocal AAHs and different zones of histologic progression within AISs and MIAs. Multiregion sequencing demonstrated different genetic drivers within the same tumour and reveal that clonal expansion is an early event of tumorigenesis. We find that KRAS, TP53 and EGFR mutations are indicators of malignant transition. Utilizing droplet digital PCR, we find alterations associated with early neoplasms in paired circulating DNA. This study provides insight into the heterogeneity of clonal events in the progression of early lung neoplasia and demonstrates that these events can be detected even before neoplasms have invaded and acquired malignant potential.

Suggested Citation

  • Evgeny Izumchenko & Xiaofei Chang & Mariana Brait & Elana Fertig & Luciane T. Kagohara & Atul Bedi & Luigi Marchionni & Nishant Agrawal & Rajani Ravi & Sian Jones & Mohammad O. Hoque & William H. West, 2015. "Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9258
    DOI: 10.1038/ncomms9258
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    Cited by:

    1. Zhoufeng Wang & Zhe Li & Kun Zhou & Chengdi Wang & Lili Jiang & Li Zhang & Ying Yang & Wenxin Luo & Wenliang Qiao & Gang Wang & Yinyun Ni & Shuiping Dai & Tingting Guo & Guiyi Ji & Minjie Xu & Yiying , 2021. "Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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