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Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer

Author

Listed:
  • Jingying Nong

    (Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute)

  • Yuhua Gong

    (Geneplus-Beijing
    Geneplus-Beijing Institute)

  • Yanfang Guan

    (Geneplus-Beijing
    Geneplus-Beijing Institute)

  • Xin Yi

    (Geneplus-Beijing
    Geneplus-Beijing Institute)

  • Yuting Yi

    (Geneplus-Beijing
    Geneplus-Beijing Institute)

  • Lianpeng Chang

    (Geneplus-Beijing
    Geneplus-Beijing Institute)

  • Ling Yang

    (Geneplus-Beijing
    Geneplus-Beijing Institute)

  • Jialin Lv

    (Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute)

  • Zhirong Guo

    (Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute)

  • Hongyan Jia

    (Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute)

  • Yuxing Chu

    (Geneplus-Beijing)

  • Tao Liu

    (Geneplus-Beijing
    Geneplus-Beijing Institute)

  • Ming Chen

    (Zhejiang Cancer Hospital)

  • Lauren Byers

    (University of Texas MD Anderson Cancer Center)

  • Emily Roarty

    (University of Texas MD Anderson Cancer Center)

  • Vincent K. Lam

    (University of Texas MD Anderson Cancer Center)

  • Vassiliki A. Papadimitrakopoulou

    (University of Texas MD Anderson Cancer Center)

  • Ignacio Wistuba

    (University of Texas MD Anderson Cancer Center)

  • John V. Heymach

    (University of Texas MD Anderson Cancer Center)

  • Bonnie Glisson

    (University of Texas MD Anderson Cancer Center)

  • Zhongxing Liao

    (University of Texas MD Anderson Cancer Center)

  • J. Jack Lee

    (University of Texas MD Anderson Cancer Center)

  • P. Andrew Futreal

    (University of Texas MD Anderson Cancer Center)

  • Shucai Zhang

    (Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute)

  • Xuefeng Xia

    (Houston Methodist Research Institute)

  • Jianjun Zhang

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

  • Jinghui Wang

    (Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute)

Abstract

Subclonal architecture and genomic evolution of small-cell lung cancer (SCLC) under treatment has not been well studied primarily due to lack of tumor specimens, particularly longitudinal samples acquired during treatment. SCLC is characterized by early hematogenous spread, which makes circulating cell-free tumor DNA (ctDNA) sequencing a promising modality for genomic profiling. Here, we perform targeted deep sequencing of 430 cancer genes on pre-treatment tumor biopsies, as well as on plasma samples collected prior to and during treatment from 22 SCLC patients. Similar subclonal architecture is observed between pre-treatment ctDNA and paired tumor DNA. Mean variant allele frequency of clonal mutations from pre-treatment ctDNA is associated with progression-free survival and overall survival. Pre- and post-treatment ctDNA mutational analysis demonstrate that mutations of DNA repair and NOTCH signaling pathways are enriched in post-treatment samples. These data suggest that ctDNA sequencing is promising to delineate genomic landscape, subclonal architecture, and genomic evolution of SCLC.

Suggested Citation

  • Jingying Nong & Yuhua Gong & Yanfang Guan & Xin Yi & Yuting Yi & Lianpeng Chang & Ling Yang & Jialin Lv & Zhirong Guo & Hongyan Jia & Yuxing Chu & Tao Liu & Ming Chen & Lauren Byers & Emily Roarty & V, 2018. "Circulating tumor DNA analysis depicts subclonal architecture and genomic evolution of small cell lung cancer," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05327-w
    DOI: 10.1038/s41467-018-05327-w
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    Cited by:

    1. Ming Chen & Runzhe Chen & Ying Jin & Jun Li & Xin Hu & Jiexin Zhang & Junya Fujimoto & Shawna M. Hubert & Carl M. Gay & Bo Zhu & Yanhua Tian & Nicholas McGranahan & Won-Chul Lee & Julie George & Xiao , 2021. "Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. David Hsiehchen & Leslie Bucheit & Dong Yang & Muhammad Shaalan Beg & Mir Lim & Sunyoung S. Lee & Pashtoon Murtaza Kasi & Ahmed O. Kaseb & Hao Zhu, 2022. "Genetic features and therapeutic relevance of emergent circulating tumor DNA alterations in refractory non-colorectal gastrointestinal cancers," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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