Next-Generation Sequencing Enhances the Diagnosis Efficiency in Thyroid Nodules

Abstract

BackgroundThough fine-needle aspiration (FNA) improved the diagnostic methods of thyroid nodules, there are still parts of nodules that cannot be determined according to cytology. In the Bethesda system for reporting thyroid cytopathology, there are two uncertain cytology results. Thanks to the development of next-generation sequencing technology, it is possible to gain the genetic background of pathological tissue efficiently. Therefore, a combination of the cytology and genetic background may enhance the accuracy of diagnosis in thyroid nodules.MethodsDNA from 73 FNA samples of thyroid nodules belonging to different cytology types was extracted and exome sequencing was performed by the ThyroLead panel. Test for BRAF mutation was also performed by ARMS-qPCR. Information including age, sex, preoperative cytology, BRAF mutation status tested by ARMS-qPCR, and surgical pathology was collected in electronic medical record system.ResultsA total of 71 single nucleotide variants, three fusion gene, and two microsatellite instability-high status were detected in 73 FNA samples. BRAF V600E mutation is the most common mutation in these malignant thyroid nodules. After combining the cytology and genetic background detected by next-generation sequencing, the diagnosis sensitivity was increased from 0.582 (95% CI: 0.441–0.711) to 0.855 (95% CI: 0.728–0.930) (P < 0.001) in our group, while the specificity, 1,000 (95% CI: 0.732–1.000) compared to 0.857 (95% CI: 0.562–0.975) (P = 0.25), did not get affected.ConclusionsNext-generation sequencing in thyroid nodules can enhance the preoperative diagnosis sensitivity by fine-needle aspiration alone. It can also provide genetic background for direction of medication. It is possible for clinicians to combine cytology with genetic alterations for a more precise diagnosis strategy of thyroid nodules.

Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea

“…NGS could make it possible to obtain parallel sequencing of multiple genes rapidly. Thus, it could be helpful for differentiating thyroid cancer from a benign nodule and for identifying actionable targets in advanced thyroid cancer, emphasizing ‘precision medicine [ 23 , 24 , 25 , 26 ]. Although there is no clear guideline for application of NGS in advanced thyroid cancer, NGS could be useful for detecting the RET fusion gene [ 25 , 27 , 28 ].…”

Fusion Oncogenes in Patients With Locally Advanced or Distant Metastatic Differentiated Thyroid Cancer

“…The ThyroLead panel (Topgen, China) covering the exonic region of 18 genes ( HRAS, KRAS, NRAS, CDC73, CDKN1B, DICER1, IDH1, MEN1, MTOR, PIK3CA, PTEN, TP53, TSHR, CTNNB1, GNAS, PAX8, AKT1, EIF1AX ), a 1000-bp region in the promoter region of TERT , and both exonic and intronic regions for 7 fusion oncogenes ( BRAF, RET, NTRK1/2/3, ALK, and PPARG ), was used in our study. The details of DNA isolation, sequence library preparation, and sequencing were described in a previous study ( 56 ). Adapter sequences and low-quality reads (with more than 40% of bases failing Q25; reads <70 bp; and low-complexity reads) were removed by Fastp.…”

Next-Generation sequencing genomic landscape of Chinese thyroid tumors

“…The incidence of two types of uncertain cytology is about 10% [17] which leads to a dilemma in clinical decisions. To solve this dilemma, strategies have been proposed that combine cytopathology with molecular patterns of FNA samples to improve diagnostic accuracy [19][20][21][22] A total of 695 samples of this study were FNA. There were 42 Bethesda grade 1 nodules, 134 Bethesda grade 2 nodules, 114 Bethesda grade 3 or 4 nodules, and 391 Bethesda grade 5 or 6 nodules.…”