Molecular Biology of Thyroid Cancer and Their Clinical Applications

Abstract

Thyroid cancer is the most common endocrine malignancy, with papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) being the predominant subtypes. Recent advancements in molecular biology have significantly improved our understanding of thyroid carcinogenesis, leading to novel diagnostic and therapeutic strategies. Key genetic alterations, including BRAF, RAS, RET/PTC fusions, and PAX8-PPARγ rearrangements, play crucial roles in tumor initiation and progression. BRAF mutations, particularly BRAFV600E, are strongly associated with aggressive PTC phenotypes, whereas RAS mutations are prevalent in follicular-patterned thyroid tumors. Poorly differentiated and anaplastic thyroid carcinomas harbor mutations in TP53, TERT promoter, and components of the MAPK and PI3K pathways, contributing to their aggressive behavior. Advances in molecular diagnostics, such as next-generation sequencing and gene expression classifiers, have enhanced the accuracy of thyroid nodule evaluation, reducing unnecessary surgeries. This review provides an in-depth analysis of the molecular mechanisms underlying thyroid cancer and their clinical applications, emphasizing the role of molecular testing in risk stratification, prognostication, and personalized treatment approaches.

[N A J Med Sci. 2025;18(1):038-048.   DOI:  10.7156/najms.2025.1801038]

Key Words: Molecular biology, thyroid cancer, RET, RAS, BRAF, clinical applications