UNASSIGNED: Thyroid cancer rarely occurs in children and adolescents. Molecular markers such as BRAF, RAS, and RET/PTC have been widely used in adult PTC. It is currently unclear whether these molecular markers have equivalent potential for application in pediatric patients. This study aims to explore the potential utility of a multi-gene conjoint analysis based on next-generation targeted sequencing for pediatric papillary thyroid carcinoma (PTC).
UNASSIGNED: The patients diagnosed with PTC (aged 18 years or younger) in the pediatrics department of Lishui District Hospital of Traditional Chinese Medicine were retrospectively screened. A targeted enrichment and sequencing analysis of 116 genes associated with thyroid cancer was performed on paraffin-embedded tumor tissues and paired paracancerous tissue of fifteen children (average age 14.60) and nine adults (average age 49.33) PTC patients. Demographic information, clinical indicators, ultrasonic imaging information and pathological data were collected. The Kendall correlation test was used to establish a correlation between molecular variations and clinical characteristics in pediatric patients.
UNASSIGNED: A sample of 15 pediatric PTCs revealed a detection rate of 73.33% (11/15) for driver gene mutations BRAF V600E and RET fusion. Compared to adult PTCs, the genetic mutation landscape of pediatric PTCs was more complex. Six mutant genes overlap between the two groups, and an additional seventeen unique mutant genes were identified only in pediatric PTCs. There was only one unique mutant gene in adult PTCs. The tumor diameter of pediatric PTCs tended to be less than 4cm (p<0.001), and the number of lymph node metastases was more than five (p<0.001). Mutations in specific genes unique to pediatric PTCs may contribute to the onset and progression of the disease by adversely affecting hormone synthesis, secretion, and action mechanisms, as well as the functioning of thyroid hormone signaling pathways. But, additional experiments are required to validate this hypothesis.
UNASSIGNED: BRAF V600E mutation and RET fusion are involved in the occurrence and development of adolescent PTC. For pediatric thyroid nodules that cannot be determined as benign or malignant by fine needle aspiration biopsy, multiple gene combination testing can provide a reference for personalized diagnosis and treatment by clinical physicians.

UNASSIGNED: We aimed to investigate the mechanisms of action on Klotho that underlie cancer development in RET fusion models of human papillary thyroid cancer (PTC).
UNASSIGNED: Normal Nthy-ori 3-1 thyroid cells and two PTC cell lines (BHP10-3 and TPC-1), which were used as RET fusion models of PTC, were used to study Klotho. Klotho expression was analyzed by Western blotting. Klotho overexpression cell lines were constructed using the two types of PTC cells. Cell proliferation and apoptosis were assessed. Western blotting was used to detect the expression of proteins in the Wnt/β-catenin pathway. In addition, an activator and an inhibitor of the Wnt/β-catenin pathway were used to confirm that Klotho regulates the pathway in PTC cells. Mice were used to analyze the in vivo effect of Klotho on tumor growth and the Wnt/β-catenin pathway.
UNASSIGNED: In BHP10-3 and TPC-1 cells, Klotho expression was low. After Klotho overexpression, the cell proliferation was significantly suppressed and apoptosis was significantly increased (p<0.05). Wnt1, β-catenin, and CyclinD1 expression were also significantly decreased after Klotho overexpression (p<0.05). Administration of the Wnt/β-catenin pathway activator attenuated the effect of Klotho overexpression (p<0.05). In vivo, the tumor growth was suppressed, and apoptosis of the cancer cells in the tumors were increased after Klotho overexpression. However, injection of the Wnt/β-catenin pathway activator attenuated the effects of Klotho overexpression.
UNASSIGNED: Klotho inhibits cell proliferation in RET fusion models of PTC by inhibiting the Wnt/β-catenin pathway, providing a potential target for developing treatment for PTC.

BACKGROUND: RET/PTC rearrangements have been identified as a specific genetic event in papillary thyroid cancer (PTC). We conducted this meta-analysis to identify an enriched population who were more likely to occur RET/PTC fusion genes.
METHODS: All relevant studies in the PubMed, Web of Science, and Embase databases were searched up to June 2015. The studies found were screened according to our inclusion and exclusion criteria. All analyses were performed using STATA software.
RESULTS: Eventually, 38 eligible studies comprising 2395 participants were included. Overall analysis indicated that radiation exposure contributed to increased RET/PTC risk (OR = 2.82; 95%CI: 1.38-5.78, P = 0.005). Stratified analysis according to RET/PTC subtype and geographical area showed that this association was restricted to the RET/PTC3 subtype (OR = 8.30, 95%CI: 4.32-15.96, P < 0.001) in the Western population. In addition, age < 18 years, i.e., young age, was associated with higher prevalence of RET/PTC3 (OR = 2.03, 95%CI: 1.14-3.62, P = 0.017), especially in the radiation-exposure subpopulation (OR = 2.35, 95%CI: 1.01-5.49, P = 0.048). The association between female gender and RET/PTC1 risk was more significant in the PTC patients without radiation exposure (OR = 1.69, 95%CI: 1.04-2.74, P = 0.034).
CONCLUSIONS: Both radiation exposure and young age are associated with increased risk of RET/PTC3 and that female gender is associated with higher prevalence of RET/PTC1 in the subpopulation without radiation exposure. The RET/PTC status in combination with radiation exposure, age, and sex should be considered in the differential diagnosis of suspicious PTC.