Detection of ctDNA in the plasma of patients with papillary thyroid carcinoma

A total of 15–30% of thyroid nodules that are evaluated by fine-needle aspiration are not clearly determined to be benign or malignant. Gene mutation analysis is recommended for the evaluation of thyroid nodules using clinical guidelines. The detection of circulating tumor DNA (ctDNA) has the potential to aid in the screening, diagnosis and prediction of thyroid cancer prognosis, and can be used when tissues are difficult to obtain. In the present study, whole-exome sequencing (WES) was performed on tumors and matched normal tissues from 10 patients with papillary thyroid carcinoma (PTC) in Quanzhou, China. Hotspot mutations in tumor DNA and cell-free DNA were identified in the validation cohort, which included 59 patients with PTC. BRAF V600E occurred in five samples, and was the most frequent mutation observed. Variation allele frequency (VAF) of BRAF V600E detected by WES was positively correlated with VAF determined using digital PCR (R(2)=0.9197; P=0.0099). A number of novel mutated genes were identified, including zinc finger protein 717, pleckstrin homology like domain family A member 1, RBMX like 3, lysine methyltransferase 5A and trichohyalin, along with the reported genes BRAF, NRAS and mucin 16, cell surface associated. Somatic mutated genes were enriched in the ‘focal adhesion’ pathway, as determined by Kyoto Encyclopedia of Genes and Genomes or Gene Ontology analysis. In the validation cohort, 44.07% of tumors were BRAF V600E-positive, and the sensitivity and specificity of BRAF V600E ctDNA were 61.54 and 90.91%, respectively. BRAF V600E was associated with aggressive tumor factors, including lymph node metastasis (P=0.001) and advanced disease stage (P=0.009). The present study investigated the accuracy of ctDNA detection in patients with PTC, and provided evidence that ctDNA can be used as an evaluation of tumor DNA in thyroid nodules.