Age of Onset of Receptor Tyrosine Kinase Fusions Drives Distinct Biologic Outcomes in Thyroid Cancer

Fagin, James A.

doi:10.1200/jco.21.02864

Cited by 3 publications

(1 citation statement)

References 10 publications

(14 reference statements)

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“…In addition, an interesting tendency between the incidence of fusion oncogenes and age was observed: the younger the patients were, the higher the incidence of fusion oncogenes. Of note, when patients were subgrouped by the age of 20 years, it was found that pDTCs (years <20) had a higher incidence of fusion oncogenes (45.2% vs 25.5%) but a lower incidence of BRAF mutations (19.4% vs 49.5%) than their adult counterparts, which is concordant with previous literature ( 47 , 58 , 59 ).…”

Section: Discussionsupporting

confidence: 90%

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

Ju,

Sun,

Wang

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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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.

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Section: Discussionsupporting

confidence: 90%

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

Ju,

Sun,

Wang

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Multi-view progression diagnosis of thyroid cancer by integrating platelet transcriptomes and blood routine tests

Lai,

Xu,

et al. 2023

Computers in Biology and Medicine

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Nodal Metastases Associated With Fusion Oncogenes Are Age Dependent in Young Adult Patients With Thyroid Cancer

Li,

Han,

Meng

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Fusion oncogenes, especially those involving RET or NTRK, are known drivers of papillary thyroid cancer (PTC). They are prevalent in pediatric patients and correlate with aggressive tumor behavior. Objective We explored the age dependence of fusion oncogenes and aggressive tumor behavior in young adult PTC patients. Experimental Design We examined 150 tumors from 142 PTC patients aged between 17∼35 years old with established tumor-node-metastasis stages. Oncogenic drivers and the thyroid differentiation score (TDS) were determined by DNA and RNA sequencing of a target panel. Transcriptome analysis was performed in PTCs with RET fusions. Results Among 150 PTCs, we detected BRAF V600E (n = 105), RET fusions (n = 15), NTRK3 fusions (n = 8), and BRAF fusions (n = 4). We found that fusion oncogenes were associated with nodal metastasis when age was tiered into 3 groups: <25 years, 25∼29 years, and 30∼35 years. Patients under 25 years old showed a marginal increase in tumor stage compared to those over 25 years (75.00% vs 21.74%, P = .0646). Risk of lateral lymph node metastasis increased with younger age (75.00% vs 27.27% vs 8.33%, P = .0369). As with advanced tumor and node stage, patients harboring fusion oncogenes and aged under 25 years showed the lowest TDS; genes associated with immunoglobulin production and production of molecular mediators of the immune response were significantly upregulated. Conclusions Adult PTC patients under 25 years with fusion oncogenes showed a tendency toward advanced tumor stage and lower thyroid differentiation. Integrating onset age together with oncogenic alterations is worthwhile when managing adult PTC patients.

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Age of Onset of Receptor Tyrosine Kinase Fusions Drives Distinct Biologic Outcomes in Thyroid Cancer

Abstract: A third possibility to explain the distinct age-dependent biologic consequences of RET and NTRK fusions may ASSOCIATED CONTENT See accompanying article on page 1081Author affiliations and support information (if applicable) appear at the end of this article.

Cited by 3 publications

References 10 publications

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

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

Multi-view progression diagnosis of thyroid cancer by integrating platelet transcriptomes and blood routine tests

Nodal Metastases Associated With Fusion Oncogenes Are Age Dependent in Young Adult Patients With Thyroid Cancer

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