Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence

Abstract

ObjectivesEsophageal 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 DesignGenomic 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.ResultsWe 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.ConclusionsThe 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.

Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence

“…could show that higher ccfDNA levels after oesophagectomy are associated with poorer disease free survival of oesophageal squamous cell carcinoma patients 19 . Similar results were obtained by Ueda et al ., who describe the usage of somatic mutations in ccfDNA as a biomarker for post-surgical oesophageal squamous cell carcinoma recurrence 20 . The application of mutational analysis on ccfDNA for monitoring treatment effects and early detection of oesophageal squamous cell carcinoma was also depicted by Luo et al .…”

Machine learning to predict early recurrence after oesophageal cancer surgery

“…Combining these factors could potentially increase the performance of our model if incorporated in the future. Ultimately, differential gene expression and mutation 44,45 may well determine prognostication and treatment pathways 46 , but we are likely years from this being universally available. Until then clinical and histopathological data remains the gold standard.…”

Circulating tumor DNA analysis in the era of precision oncology

“…In another study, high concordance of multiple somatic mutations was found between plasma ctDNA and tumor (primary or metastases) DNA (83%-100%). The allele frequencies of the mutations increased with tumor burden and preceded radiologic evidence of tumor recurrence by 6 months [34]. www.oncotarget.com In 29 patients with localized esophageal carcinoma treated with chemoradiotherapy, baseline ctDNA levels (NGS-based CAPP-seq) were correlated with metabolic tumor volume and squamous histology.…”