Related Experiment Video
Updated: Jan 27, 2026
Transoral Robotic Total Thyroidectomy and Bilateral Central Regional Lymph Node Dissection for Papillary Thyroid Carcinoma
Published on: September 15, 2023
AGK-BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma
Luiza Sisdelli1, Maria Isabel Cunha Vieira Cordioli1, Fernanda Vaisman2
1Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
Insights
Pediatric papillary thyroid carcinoma (PTC) shows distinct BRAF alterations. AGK-BRAF fusions are linked to younger age and metastasis, while BRAF V600E mutations correlate with older age and larger tumors.
Area of Science:
- Oncology
- Genetics
- Pediatric Medicine
Background:
- Thyroid carcinoma incidence is rising, particularly in pediatric patients, predominantly as papillary thyroid carcinoma (PTC).
- Mitogen-activated protein kinase (MAPK) pathway alterations, including BRAF V600E mutations and BRAF fusions, are common in PTC.
- While BRAF V600E is prevalent in adult PTC, BRAF fusions are more common in pediatric PTC, but their prognostic significance remains unclear.
Purpose of the Study:
- To investigate the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in pediatric PTC.
- To correlate these genetic alterations with clinicopathological features in pediatric PTC patients.
- To understand the prognostic implications of different BRAF alterations in pediatric thyroid cancer.
Main Methods:
- Analysis of a large cohort of predominantly sporadic pediatric PTC cases.
- Detection of somatic AGK-BRAF fusion using RT-PCR and FISH break-apart.
- Screening for BRAF V600E mutation via Sanger sequencing.
Main Results:
- AGK-BRAF fusion was identified in 19% of pediatric PTC cases, associated with distant metastasis and younger patient age.
- BRAF V600E mutation was found in 15% of pediatric PTC cases, correlated with older age and larger tumor size.
- Distinct clinicopathological correlations were observed for AGK-BRAF fusion versus BRAF V600E mutation.
Conclusions:
- BRAF alterations play a significant role in the genetic landscape of pediatric PTC.
- AGK-BRAF fusions and BRAF V600E mutations have different clinical associations in pediatric thyroid cancer.
- Findings may inform future diagnostic, prognostic, and therapeutic strategies for pediatric PTC.
Background:
The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen-activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation-exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC.
Procedure:
In this study, we investigated the prevalence of BRAF alterations (AGK-BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK-BRAF fusion was investigated by RT-PCR and confirmed by FISH break-apart. The BRAF V600E mutation was screened using Sanger sequencing.
Results:
AGK-BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size.
Conclusion:
Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.
Related Concept Videos
01:11Papillary Dermis
The dermis might be considered the "core" of the integumentary system, as distinct from the epidermis and hypodermis. It contains blood and lymph vessels, nerves, and other structures, such as hair follicles and sweat glands. The dermis is made of two layers of connective tissue that comprise an interconnected mesh of elastin and collagenous fibers, produced by fibroblasts.
Papillary Layer
The papillary layer is made of loose, areolar connective tissue, which means the collagen...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:23The Thyroid Gland
The follicles have a central cavity lined by simple cuboidal to squamous epithelial cells called follicular cells. These cells produce the glycoprotein...
01:26Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
01:18Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
01:19The Effect of Aging on Tissues