Molecular pathogenesis of pediatric thyroid carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Pediatric Cancer Research

Background:

• Pediatric thyroid cancers, primarily papillary thyroid carcinoma (PTC), have poorly understood molecular drivers.
• Ionizing radiation is a significant environmental risk factor for pediatric PTC, particularly evident after the Chernobyl accident.
• Advances in diagnostic imaging have increased the identification of sporadic pediatric PTC cases, offering new insights.

Purpose of the Study:

• To summarize recent molecular findings in sporadic and radiation-associated pediatric PTC.
• To elucidate the roles of specific genetic alterations in pediatric PTC development.
• To explore the relationship between age, radiation exposure, and driver oncogene mutations in pediatric PTC.

Main Methods:

• Review of recent literature on molecular pathogenesis of pediatric PTC.
• Analysis of genetic alterations including fusion oncogenes (RET/PTC) and point mutations (BRAFV600E).
• Investigation of Telomerase reverse transcriptase gene (TERT) promoter mutations and expression in pediatric PTC.

Main Results:

• Fusion oncogenes (RET/PTC) are more prevalent in younger pediatric PTC patients and those exposed to radiation.
• BRAFV600E mutations become more common in adolescent sporadic PTC, suggesting a shift in driver oncogene prevalence with age.
• While TERT promoter mutations are absent in pediatric PTC, TERT expression may still contribute to tumor aggressiveness.

Conclusions:

• Fusion oncogenes are associated with both age and radiation in pediatric PTC, but not definitive proof of exposure.
• The molecular landscape of pediatric PTC differs from adult cases, particularly regarding TERT promoter mutations.
• Understanding these molecular differences is crucial for advancing diagnosis and treatment of pediatric thyroid cancers.