Open AccessMonitoring of cancer patients via next‐generation sequencing of patient‐derived circulating tumor cells and tumor DNA
Author(s) -
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
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14092
Subject(s) - liquid biopsy , colorectal cancer , cancer , circulating tumor cell , medicine , cancer research , dna sequencing , biopsy , dna , pathology , oncology , biology , metastasis , genetics
Abstract Liquid biopsy of circulating tumor cells ( CTC ) and circulating tumor DNA (ct DNA ) is gaining attention as a method for real‐time monitoring in cancer patients. Conventional methods based upon epithelial cell adhesion molecule (Ep CAM ) 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 Ep CAM expression. In this study, we optimized a method for analyzing genetic alterations using next‐generation sequencing ( NGS ) of extracted ct DNA 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 ct DNA . We also detected time‐dependent genetic alterations that appeared during anti– EGFR therapy in CTC and ct DNA 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 ct DNA . The study was registered with the University Hospital Medical Information Network Clinical Trials Registry ( ID : UMIN 000014095).