Targeted sequencing of circulating cell-free DNA in stage II-III resectable oesophageal squamous cell carcinoma patients.
Adult
Aged
Base Sequence
/ genetics
Biomarkers, Tumor
/ genetics
Circulating Tumor DNA
/ genetics
Cohort Studies
Esophageal Neoplasms
/ blood
Esophageal Squamous Cell Carcinoma
/ blood
Female
Follow-Up Studies
Gene Frequency
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasm Recurrence, Local
/ genetics
Neoplasm Staging
Postoperative Period
Preoperative Period
Circulating cell-free DNA
Next-generation sequencing
Oesophageal squamous cell carcinoma
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
20 Aug 2019
20 Aug 2019
Historique:
received:
12
04
2018
accepted:
08
08
2019
entrez:
21
8
2019
pubmed:
21
8
2019
medline:
26
2
2020
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31429737
doi: 10.1186/s12885-019-6025-2
pii: 10.1186/s12885-019-6025-2
pmc: PMC6701116
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
818Subventions
Organisme : National Natural Science Foundation of China
ID : 81872334
Organisme : National Natural Science Foundation of China
ID : 81200712
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