Targeted Mutational Profiling and a Powerful Risk Score as Additional Tools for the Diagnosis of Papillary Thyroid Cancer

Abstract

Nowadays, the complementary diagnostics based on the suspicious thyroid lesion specific mutational state analysis is indispensable in the clinical practice. We aimed to test and validate our novel 568-mutational hotspot panel (23 cancer-related genes) on papillary thyroid cancers (PTCs) and their tumor-free pairs to find the most powerful mutation pattern related to PTC. The sequencing method was carried on with Ion Torrent PGM on 67 thyroid tissue samples. The most commonly detected mutation was the BRAF c.1799 T > A in all non-classical PTC cases. We utilized a multivariate statistical method (CVA) to determine a discrimination score based on mutational data array and to assess malignancy risk. Based on variants, the BRAF gene has by far the highest indicative power, followed by TSHR and APC. We highlighted novel aspects of the mutational profile and genetic markers of PTC. CVA has correctly assigned most of the samples based on the mutation frequencies and different variables of the selected genes, with high analytical probabilities. The final goal is to set up a new comprehensive rule-in and rule-out test to support the clinical decision making mainly in inconclusive fine-needle aspiration biopsy cases.

Competing-Risks Model for Predicting the Postoperative Prognosis of Patients with Papillary Thyroid Adenocarcinoma Based on The Surveillance, Epidemiology, and End Results (SEER) Database

“…Thyroid nodules cancer is the most common endocrine malignancy [ 1 ], constituting 2–3% of all new cancers diagnosed each year in the USA, and its incidence worldwide has been steadily increasing for more than 30 years [ 2 ]. Thyroid cancer is most frequently diagnosed in females aged 45–55 years, and the risk factors include a personal history of head and neck radiation exposure and a family history of thyroid cancer [ 3 ].…”

Molecular testing in indeterminate thyroid nodules: an additional tool for clinical decision-making

“…Considering a cancer prevalence of 22.5%, the NGS panel had a SN of 89% and a NPV of 96% and the miRNA assay had a SP of 93% and PPV of 93%. Kocsis-Deák and colleagues 70 designed a 23-gene and 568-mutational hotspot panel encompassing MAPK/PI3K/AKT signalling paired with a mutation risk score to assess risk of malignancy of PTC. Ke and colleagues 71 developed the tyroline NGS panel, detecting 15 target gene mutations and 2 fusions.…”