한빛사논문
- 조회395
Jee-Soo Lee,a Youngmin Han,b Won-Gun Yun,b Wooil Kwon,b Hongbeom Kim,b Hyeonju Jeong,a Myoung-Seock Seo,a Yongsook Park,a Sung Im Cho,a Haeryoung Kim,c Ji Yeon Kim,d Moon-Woo Seong,a,d Jin-Young Jang,b,* and Sung Sup Parka,d,*
aDepartment of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea;
bDepartment of Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea;
cDepartment of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea;
dBiomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
*Address correspondence to: S.S.P. ; J.-Y.J.
Abstract
Background: Circulating tumor DNA (ctDNA) is a promising biomarker for early tumor detection and minimal residual disease (MRD) assessment in early-stage cancer, but quantifying minute amounts of ctDNA is challenging and well-designed studies on ctDNA in early-stage cancer are still lacking. Here, we adapted a sensitive next-generation sequencing (NGS) technology and performed parallel analysis of pre- and postoperative ctDNA and matched tumor tissues in a prospective cohort of patients with resectable pancreatic ductal adenocarcinoma (PDAC).
Methods: In total, 70 consecutive patients undergoing curative resection for resectable PDAC were enrolled. We performed integrated digital error suppression-enhanced cancer personalized profiling by deep sequencing NGS of triple-matched samples (pre/postoperative plasma cell-free DNA [cfDNA], tumor tissue, and genomic DNA) targeting 77 genes.
Results: Preoperative ctDNA was detected in 37.7% of the evaluable patients, with a median variant allele frequency of 0.09%. Twelve additional oncogenic mutations were detected exclusively in preoperative ctDNA but not in tissue. When quantitative concentrations of ctDNA were estimated in haploid genome equivalents per milliliter (hGE/mL), the risk of early recurrence was high in patients with postoperative ctDNA >1 hGE/mL. cfDNA variants from 24.5% of patients had features compatible with clonal hematopoiesis.
Conclusions: An optimized NGS approach might add value beyond tissue analysis through the highly sensitive detection of minute amounts of ctDNA in resectable PDAC. Postoperative ctDNA concentration could be a tool for MRD assessment. Moreover, parallel analyses of matched tissues and leukocytes might be required to accurately detect clinically relevant ctDNA.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2022-12-29)
- 국내 연구진
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