Monitoring of cancer patients via next‐generation sequencing of patient‐derived circulating tumor cells and tumor DNA. Issue 8 (23rd July 2019)

• Record Type: Journal Article
• Authors: Onidani, Kaoru; Shoji, Hirokazu; Kakizaki, Takahiko; Yoshimoto, Seiichi; Okaya, Shinobu; Miura, Nami; Sekikawa, Shoichi; Furuta, Koh; Lim, Chwee Teck; Shibahara, Takahiko; Boku, Narikazu; Kato, Ken; Honda, Kazufumi
• Is Part Of: Cancer science. Volume 110:Issue 8(2019)
• Page Start: 2590
• Page End: 2599
• Publication Date: 2019-07-23
• Subjects: circulating tumor cell -- circulating tumor DNA -- gastrointestinal cancer -- head and neck cancer -- liquid biopsy; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14092
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Liquid biopsy of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) is gaining attention as a method for real‐time monitoring in cancer patients. Conventional methods based upon epithelial cell adhesion molecule (EpCAM) expression have a risk of missing the most aggressive CTC subpopulations due to epithelial‐mesenchymal transition and may, thus, underestimate the total number of actual CTC present in the bloodstream. Techniques utilizing a label‐free inertial microfluidics approach (LFIMA) enable efficient capture of CTC without the need for EpCAM expression. In this study, we optimized a method for analyzing genetic alterations using next‐generation sequencing (NGS) of extracted ctDNA and CTC enriched using an LFIMA as a first‐phase examination of 30 patients with head and neck cancer, esophageal cancer, gastric cancer and colorectal cancer (CRC). Seven patients with advanced CRC were enrolled in the second‐phase examination to monitor the emergence of alterations occurring during treatment with epidermal growth factor receptor (EGFR)‐specific antibodies. Using LFIMA, we effectively captured CTC (median number of CTC, 14.5 cells/mL) from several types of cancer and detected missense mutations via NGS of CTC and ctDNA. We also detected time‐dependent genetic alterations that appeared during anti–EGFR therapy in CTC and ctDNA from CRC patients. The results of NGS analyses indicated that alterations in the genomic profile revealed by the liquid biopsy could be expanded by using a combination of assays with CTC and ctDNA. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (ID: UMIN000014095). Abstract : In summary, we optimized the efficiency of a platform for capturing circulating tumor cells (CTC) using a label‐free inertial microfluidics approach and revealed the importance of both CTC and circulating tumor DNA (ctDNA) as diagnostic tools. In addition, our data suggest that both CTC and ctDNA can be used to closely monitor the emergence of molecular changes in patients with metastatic colorectal cancer.