The role of epigenetic alterations in papillary thyroid carcinogenesis

Papillary thyroid carcinoma (PTC) accounts for over 80% of all thyroid malignancies. The molecular pathogenesis remains incompletely clarified although activation of the RET fusion oncogenes, and RAS and BRAF oncogenes, has been well characterized. Novel technologies using genome-wide approaches to study tumor genomes and epigenomes have provided great insights into tumor development. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause altered patterns of gene expression/function. It has been established beyond doubt that promoter cytosine methylation in CpG islands, and the subsequent gene silencing, is intimately involved in cancer development. These epigenetic events very likely contribute to significant variation in gene expression profiling, phenotypic features, and biologic characteristics seen in PTC. Hypermethylation of promoter regions has also been analyzed in PTC, and most studies have focused on individual genes or a small cohort of genes implicated in tumorigenesis.