Genomic Characterization of Differentiated Thyroid Carcinoma

Area of Science:

• Genomics
• Molecular Biology
• Oncology

Background:

• The Cancer Genome Atlas (TCGA) study of papillary thyroid carcinoma (PTC) in 2014 spurred further genomic investigations.
• Massively-parallel sequencing (MPS) advances offer critical insights into differentiated thyroid carcinoma (DTC) molecular pathogenesis.
• DTC exhibits a low mutational burden compared to other cancers.

Purpose of the Study:

• To review genomic study results using MPS technology in DTC.
• To describe the types and frequencies of genomic alterations across DTC histological subtypes.
• To detail the characteristics and significance of DTC gene expression signatures.

Main Methods:

• Review of published genomic studies utilizing massively-parallel sequencing (MPS).
• Analysis of genomic alteration frequencies stratified by DTC histological subtypes (e.g., classical PTC, follicular variant PTC, follicular thyroid carcinoma).
• Examination of gene expression profiles and their association with molecular and clinicopathological characteristics.

Main Results:

• Recurrently altered genes in DTC include BRAF, RAS, and fusion genes, with novel driver candidates identified.
• The frequency of these genomic alterations varies significantly among DTC subtypes.
• Telomerase reverse transcriptase (TERT) promoter mutations are a major driver of DTC progression.
• DTC subtypes are classifiable by distinct gene expression profiles, mutational signatures, and intracellular signaling outputs.

Conclusions:

• MPS technology has elucidated the genomic landscape of DTC.
• Understanding the specific genomic alterations and gene expression signatures is crucial for classifying DTC subtypes and their progression.
• This review synthesizes current knowledge on DTC genomics and transcriptomics for improved molecular pathogenesis understanding.