Next-Generation Sequencing Test Promising for Diagnosis of Indeterminate Thyroid Nodules

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A next-generation sequencing panel of genetic markers may improve cancer diagnosis of indeterminate thyroid nodules.

A next-generation sequencing panel that scans for a broad number of genetic markers demonstrated more than 90% accuracy in diagnosing thyroid nodules with indeterminate cytology, according to study results presented at the 84th Annual Meeting of the American Thyroid Association.

Although fine needle aspiration (FNA) is a widely used approach to analyzing thyroid nodules, as many as 20% to 30% have indeterminate cytology, researchers wrote in an abstract. In particular, follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN) is common and estimated risk for cancer is 15% to 30%.

To determine whether a next-generation sequencing panel of genetic markers could improve cancer diagnosis in these nodules, the researchers assessed 143 consecutive FNA samples with FN/SFN cytology. Further, 91 samples with known surgical outcome were studied retrospectively and 52 prospectively.

They analyzed the samples on Ion Torrent PGM using the ThyroSeq v2 Next-Generation Sequencing panel, which tests for point mutations in the BRAF, NRAS, HRAS, KRAS, PTEN, TP53, TSHR, GNAS, CTNNB1, RET, PIK3CA, AKT1 and TERT genes and 42 gene infusions involving RET, BRAF, NTRK1, NTRK3, ALK, PPARG and THADA.

The FNA samples’ cell type composition and expression of oncogenes arising from gene fusions were examined using expression of 15 genes, according to the abstract.

Results of histologic analysis identified 104 benign and 39 malignant nodules, with a cancer rate of 27.3%. The most common point mutations affected were NRAS, KRAS, TERT and TSHR. The researchers also concurrently found NRAS and TERT mutations in two nodules. The fusions identified affected the THADA, PPARG and NTRK3 genes.

The researchers noted comparable performance characteristics between the two groups.

Sensitivity was 90% (95% CI, 80-99) and specificity was 93% (95% CI, 88-98) for the next-generation sequencing panel. Positive predictive value was 83% (95% CI, 72-95) and negative predictive value was 96% (95% CI, 92-100). Accuracy was 92% (95% CI, 88-97), the researchers reported.

“The results of this study indicate that comprehensive genotyping of thyroid nodules using a broad [next-generation sequencing] panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate optimal management of these patients,” they wrote.


  1. Nikiforov Y et al. Oral Abstract 123. Presented at: American Thyroid Association (ATA) 84th Annual Meeting; Oct. 29-Nov. 2, 2014; Coronado, Calif.