Somatic Mutational Landscape in Follicular Thyroid Cancer: Insights from AACR GENIE Data

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Follicular thyroid carcinoma (FTC) is a significant endocrine malignancy.
• Understanding the somatic mutational landscape of FTC is critical for targeted therapies.

Purpose of the Study:

• To characterize the genomic alterations in a large cohort of FTC.
• To identify molecular subtypes and potential therapeutic targets in FTC.
• To explore differences in mutational profiles between adult and pediatric, and primary and metastatic FTC.

Main Methods:

• Analysis of genomic and clinical data from 168 FTC samples obtained from the AACR Project GENIE registry via cBioPortal.
• Assessment of mutation frequencies and copy number alterations.
• Statistical comparison of mutation profiles across patient subgroups (pediatric vs. adult, primary vs. metastatic).

Main Results:

• NRAS (33.9%), TERT (22.6%), DICER1 (15.5%), HRAS (11.9%), and PTEN (10.7%) were the most frequent mutations.
• DICER1 mutations were significantly more common in pediatric FTC (44.4%) compared to adults (4.6%).
• TERT mutations were found exclusively in adults, and NRAS mutations were more prevalent in metastatic tumors.

Conclusions:

• FTC development is driven by diverse molecular pathways with notable heterogeneity.
• Significant differences in mutation profiles exist between pediatric and adult FTC, and between primary and metastatic disease.
• Molecular profiling is essential for stratifying FTC patients and guiding personalized treatment strategies.