Fusion oncogenes in patients with locally advanced or distant metastatic differentiated thyroid cancer
Gaoda Ju, Yuqing Sun, Hao Wang, Xin Zhang, Zhuanzhuan Mu, Di Sun, Lisha Huang, Ruijue Lin, Tao Xing, Wuying Cheng, Jun Liang, Yan-Song Lin- Biochemistry (medical)
- Clinical Biochemistry
- Endocrinology
- Biochemistry
- Endocrinology, Diabetes and Metabolism
Abstract
Background
Fusion oncogenes are involved in the underlying pathology of advanced differentiated thyroid cancer (DTC), and even the cause of radioactive iodine (RAI)-refractoriness. However, there is still lacking in investigation between fusion oncogenes and the clinicopathological characteristics involving a large-scale cohort of advanced DTC patients.
Methods
We collected 278 tumor samples from patients with locally advanced (N1b or T4) or distant metastatic DTC. Targeted next-generation sequencing with a 26-gene ThyroLead panel was performed on these samples.
Results
Fusion oncogenes accounted for 29.86% of the samples (72 RET fusions, 7 NTRK fusions, 4 ALK fusions) and occurred more frequently in pediatric patients than that of their adult counterparts (P = 0.003, OR: 2.411, 95% CI: 1.329-4.311) in our cohort. DTCs with fusion oncogenes appeared to have a more advanced AJCC_N and AJCC_M stage (P = 0.0002, OR: 15.47, 95% CI: 2.54-160.9, and P = 0.016, OR: 2.35, 95% CI: 1.18-4.81) compared to those without. DTCs with fusion oncogenes were associated with pediatric RAI-refractoriness compared with those without fusion oncogenes (P = 0.017, OR: 4.85, 95% CI: 1.29-15.19). However, in adult DTCs, those with fusion oncogenes were less likely to be associated with RAI-refractoriness than those without (P = 0.029, OR: 0.50, 95% CI: 0.27-0.95), owing to a high occurrence of the TERT mutation, which was the most prominent genetic risk factor for RAI-refractoriness in multivariate logistic regression analysis (P < 0.001, OR: 7.36, 95% CI: 3.14-17.27).
Conclusions
Fusion oncogenes were more prevalent in pediatric DTCs than in their adult counterparts and were associated with pediatric RAI-refractoriness, while in adult DTCs, TERT mutation was the dominant genetic contributor to RAI-refractoriness rather than fusion oncogenes.