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

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, Vincent K. Lam, Vassiliki A. Papadimitrakopoulou, Ignacio Wistuba, John V. Heymach, Bonnie Glisson, Zhongxing Liao, J. Jack Lee, P. Andrew Futreal, Shucai Zhang (), Xuefeng Xia, Jianjun Zhang () and Jinghui Wang ()
Additional contact information
Jingying Nong: Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute
Yuhua Gong: Geneplus-Beijing
Yanfang Guan: Geneplus-Beijing
Xin Yi: Geneplus-Beijing
Yuting Yi: Geneplus-Beijing
Lianpeng Chang: Geneplus-Beijing
Ling Yang: Geneplus-Beijing
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
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
Jinghui Wang: Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05327-w

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