Monitoring circulating tumor DNA by analyzing personalized cancer-specific rearrangements to detect recurrence in gastric cancer

• Published in: Experimental & molecular medicine Vol. 51; no. 8; pp. 1 - 10
• Main Authors: Kim, Young-Woo, Kim, Young-Ho, Song, Yura, Kim, Han-Seong, Sim, Hye Won, Poojan, Shiv, Eom, Bang Wool, Kook, Myeong-Cherl, Joo, Jungnam, Hong, Kyeong-Man
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.08.2019; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 38/22; 38/77; 45/23; 45/77; 631/61/514/2254; 631/67/2322; 631/67/69; Adenocarcinoma - blood; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adult; Aged; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cancer screening; Chromosome Aberrations; Circulating Tumor DNA - analysis; Circulating Tumor DNA - blood; Deoxyribonucleic acid; DNA; DNA Mutational Analysis - methods; Feasibility Studies; Female; Gastric cancer; Genomes; Humans; Male; Mastectomy; Medical Biochemistry; Medical screening; Middle Aged; Molecular Medicine; Monitoring, Physiologic - methods; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Organ Specificity - genetics; Postoperative Period; Precision Medicine - methods; Predictive Value of Tests; Retrospective Studies; Stem Cells; Stomach Neoplasms - blood; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach Neoplasms - surgery; Surgery; Whole Genome Sequencing; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/s12276-019-0292-5

Circulating tumor DNA (ctDNA) has emerged as a candidate biomarker for cancer screening. However, studies on the usefulness of ctDNA for postoperative recurrence monitoring are limited. The present study monitored ctDNA in postoperative blood by employing cancer-specific rearrangements. Personalized cancer-specific rearrangements in 25 gastric cancers were analyzed by whole-genome sequencing (WGS) and were employed for ctDNA monitoring with blood up to 12 months after surgery. Personalized cancer-specific rearrangements were identified in 19 samples. The median lead time, which is the median duration between a positive ctDNA detection and recurrence, was 4.05 months. The presence of postoperative ctDNA prior to clinical recurrence was significantly correlated with cancer recurrence within 12 months of surgery ( P  = 0.029); in contrast, no correlation was found between cancer recurrence and the presence of preoperative ctDNA, suggesting the clinical usefulness of postoperative ctDNA monitoring for cancer recurrence in gastric cancer patients. However, the clinical application of ctDNA can be limited by the presence of ctDNA non-shedders (42.1%, 8/19) and by inconsistent postoperative ctDNA positivity. Cancer: Tell-tale signs of recurrence Fragments of tumor DNA, or circulating tumor DNA (ctDNA), in blood can help predict stomach cancer recurrence within 12 months of surgery. Kyeong-Man Hong at the National Cancer Center, in Goyang-si, South Korea, and colleagues, carried out whole genome sequencing of stomach tumor samples from 25 patients to identify personalized cancer-specific rearranged DNA sequences. When they used this information to monitor ctDNA in blood samples obtained after surgical removal of the tumor, they found a significant correlation between the presence of ctDNA and cancer recurrence. In most cases, ctDNA was detected around four months prior to clinical recurrence, highlighting the potential usefulness of ctDNA monitoring. The lack of correlation between ctDNA levels and tumor size suggests that further research into the factors determining ctDNA levels is needed.