DNA methylation analysis of multiple genes in thymic epithelial tumors

Aim: To investigate DNA methylation levels of a panel of genes in thymic epithelial tumors (TETs).
Materials & methods: We selected 15 genes among the most promising epigenetic biomarkers of TETs and evaluated their methylation levels in 71 TET samples.
Results: thymic carcinomas (TCs) showed hypermethylation of GHSR and ELF3 genes and reduced IL1RN methylation levels compared with thymomas (TMs) and healthy thymic tissues. RAG1 was hypomethylated in TMs compared with healthy thymic tissues. No difference in the methylation levels of the investigated genes was seen among TM stages and subtypes. No changes in blood methylation levels of the investigated genes were seen among TET subtypes.
Conclusion: The present study confirms GHSR, ELF3, IL1RN and RAG1 as TET epigenetic biomarkers.
Tumors arising from the epithelium of the thymus gland (TETs), including thymomas (TMs) and thymic carcinomas (TCs), are rare malignancies whose etiology remains almost unknown.
Recent studies are suggesting that altered epigenetic mechanisms, such as DNA methylation, contribute to TETs pathogenesis.
Altered DNA methylation levels of specific genes have been associated with the severity of TETs, potentially providing biomarkers of these conditions.
In the current study methylation levels of 15 genes among the most promising epigenetic biomarkers of TETs were evaluated in a cohort of 71 bioptic TET samples, including 64 TMs and 7 TCs.
We observed that TCs were characterized by hypermethylation of GHSR and ELF3 genes and reduced IL1RN methylation levels compared with TMs and healthy thymic tissues. Moreover, RAG1 was hypomethylated in TMs compared with healthy thymic tissues.
Since almost 20–40% of TM patients have myasthenia gravis, we also searched for differences between patients with and without MG. None of the 15 investigated genes showed mean methylation differences between the two TMs groups.
No difference in the methylation levels of the investigated genes was seen among TM stages and subtypes, and between primary tumors and recurrences.
No changes in blood methylation levels of the investigated genes were observed among TET subtypes.