Targeted sequencing of circulating cell-free DNA in stage II-III resectable oesophageal squamous cell carcinoma patients
Pei Meng,
Jiacong Wei,
Yiqun Geng,
Shaobin Chen,
Miente Martijn Terpstra,
Qiongyi Huang,
Qian Zhang,
Zuoqing Su,
Wanchun Yu,
Min Su,
Klaas Kok,
Anke van den Berg,
Jiang Gu
Affiliations
Pei Meng
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Jiacong Wei
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Yiqun Geng
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Shaobin Chen
Department of Thoracic surgery, Cancer Hospital of Shantou University
Miente Martijn Terpstra
Department of Genetics, University of Groningen, University Medical Centre Groningen
Qiongyi Huang
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Qian Zhang
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Zuoqing Su
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Wanchun Yu
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Min Su
Department of Pathology & Institute of Clinical Pathology, Shantou University Medical College
Klaas Kok
Department of Genetics, University of Groningen, University Medical Centre Groningen
Anke van den Berg
Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen
Jiang Gu
Provincial Key laboratory of Infectious Diseases and Molecular Pathology, Department of Pathology and Pathophysiology, Collaborative and Creative Centre, Shantou University Medical College
Abstract Background The aim of this study was to investigate the potential of cell-free DNA (cfDNA) as a disease biomarker in oesophageal squamous cell carcinoma (ESCC) that can be used for treatment response evaluation and early detection of tumour recurrence. Methods Matched tumour tissue, pre- and post-surgery plasma and WBCs obtained from 17 ESCC patients were sequenced using a panel of 483 cancer-related genes. Results Somatic mutations were detected in 14 of 17 tumour tissues. Putative harmful mutations were observed in genes involved in well-known cancer-related pathways, including PI3K-Akt/mTOR signalling, Proteoglycans in cancer, FoxO signalling, Jak-STAT signalling, Chemokine signalling and Focal adhesion. Forty-six somatic mutations were found in pre-surgery cfDNA in 8 of 12 patients, with mutant allele frequencies (MAF) ranging from 0.24 to 4.91%. Three of the 8 patients with detectable circulating tumour DNA (ctDNA) had stage IIA disease, whereas the others had stage IIB-IIIB disease. Post-surgery cfDNA somatic mutations were detected in only 2 of 14 patients, with mutant allele frequencies of 0.28 and 0.36%. All other somatic mutations were undetectable in post-surgery cfDNA, even in samples collected within 3–4 h after surgery. Conclusion Our study shows that somatic mutations can be detected in pre-surgery cfDNA in stage IIA to IIIB patients, and at a lower frequency in post-surgery cfDNA. This indicates that cfDNA could potentially be used to monitor disease load, even in low disease-stage patients.
