Journal
ONCOTARGET
Volume 7, Issue 38, Pages 62280-62291Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11409
Keywords
esophageal squamous cell carcinoma; cell-free DNA; next-generation sequencing; tumor recurrence; somatic mutation
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Funding
- Funding Program for Next Generation World-Leading Researchers [LS094]
- [26461980]
- [26670608]
- [26861003]
- [15H04921]
- [15H05791]
- [15K10168]
- [15K10170]
- Grants-in-Aid for Scientific Research [15H05912] Funding Source: KAKEN
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Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies owing to the high frequency of tumor recurrence. The identification of markers for early ESCC diagnosis and prediction of recurrence is expected to improve the long-term prognosis. Therefore, we searched for associations between tumor recurrence and cell-free DNA (cfDNA) mutations in blood plasma, which contains genetic markers for various cancer types. Experimental Design: Genomic DNA from tumors and cfDNA from plasma were obtained from 13 patients undergoing treatment for newly diagnosed ESCC. Next-generation sequencing of cfDNA in plasma was performed to identify mutations in 53 cancer-related genes, in which recurrent mutations were previously detected in ESCC. cfDNA mutational profiles were compared before and after tumor resection in four patients. Furthermore, somatic mutations in serial plasma samples were monitored after treatment in four patients. Results: We identified multiple concordant somatic mutations in cfDNA and primary tumor samples from 10 patients (83.3%) and in cfDNA and metastatic tumor samples from one patient (100%). Furthermore, the allele frequency of the concordant mutations in cfDNA changed concomitantly with tumor burden and increased approximately 6 months earlier than the detection of tumor recurrences by imaging tests in two patients. Conventional biomarkers, such as SCC and p53-Ab, did not reflect tumor recurrences. Conclusions: The present multigene panel, which enabled the diagnosis of tumor recurrence with greater accuracy than did using standard tumor markers or imaging methods, is expected to greatly facilitate standard, postoperative follow-up monitoring in ESCC.
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