Association between DNA methylation profile and malignancy in follicular-patterned thyroid neoplasms

Area of Science:

• Oncology
• Epigenetics
• Thyroid Cancer Research

Background:

• Differentiating benign follicular thyroid adenoma (FTA) from malignant follicular thyroid carcinoma (FTC) presents a diagnostic challenge.
• Understanding the molecular basis, particularly epigenetic alterations, is crucial for accurate diagnosis and treatment.

Purpose of the Study:

• To investigate genome-wide DNA methylation profiles in follicular thyroid carcinoma (FTC) compared to follicular thyroid adenoma (FTA) and normal thyroid (NT) tissues.
• To identify differentially methylated CpGs (DMCpGs) and associated genes in FTC and explore their relationship with gene expression.

Main Methods:

• Genome-wide DNA methylation profiling using CpG arrays on FTA (n=10), FTC (n=11), and normal thyroid (NT) (n=7) tissues.
• Principal component analysis (PCA) to assess methylation profile clustering.
• RNA sequencing (RNAseq) for transcriptome profiling and correlation with methylation data.

Main Results:

• FTC tissues showed 3,564 differentially methylated CpGs (DMCpGs) compared to NT, with 84% being hypermethylated.
• FTA methylation profiles occupied an intermediate position between FTC and NT.
• A significant number of FTC-associated hypermethylated genes were linked to Polycomb repressor complex targets and bivalent chromatin domains.
• 7.9% of DMCpG-associated genes exhibited differential expression in FTC compared to NT.

Conclusions:

• Perturbed DNA methylation, particularly hypermethylation, is a key molecular mechanism in follicular thyroid carcinoma (FTC) development.
• DNA methylation profiling holds potential as a tool to differentiate FTC from its benign counterpart, FTA.