Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations

Abstract

Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of various cancer entities. However, little is known about the role of epigenetic modifications in TENs. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms thymoma, thymic carcinoma, thymic epithelial neoplasm, epigenetics, DNA methylation, HDAC and miRNA were employed and we were able to identify forty studies focused on TENs and published between 1997 and 2021. Aberrant epigenetic alterations seem to be involved in the tumorigenesis of thymomas and thymic carcinomas, with numerous studies reporting on non-coding RNA clusters and altered gene methylation as possible biomarkers in different types of TENs. Interestingly, Histone Deacetylase Inhibitors have shown potent antitumor effects in clinical trials, thus possibly representing effective epigenetic therapeutic agents in TENs. Additional studies in larger patient cohorts are, nevertheless, needed to verify the clinical utility and safety of novel epigenetic agents in the treatment of patients with TENs.

Unraveling the Role of Histone Variant CENP-A and Chaperone HJURP Expression in Thymic Epithelial Neoplasms

“…Currently, the standard first line therapy for early-stage detectable TET is thymectomy. More advanced stage tumors are treated with chemotherapy after surgery, especially in the case of incomplete tumor resection [ 19 ]. Several studies have tried to evaluate the role of potential biomarkers in TETs, aiming also to identify potential therapeutic targets in these tumors [ 19 ].…”

“…More advanced stage tumors are treated with chemotherapy after surgery, especially in the case of incomplete tumor resection [ 19 ]. Several studies have tried to evaluate the role of potential biomarkers in TETs, aiming also to identify potential therapeutic targets in these tumors [ 19 ]. Aberrant epigenetic alterations seem to be involved in the pathogenesis of thymomas and thymic carcinomas [ 19 ]; however, the possible role epigenetic regulators, such as histone variants, histone modifications and their related chromatin remodelers remains largely unexplored.…”

“…Several studies have tried to evaluate the role of potential biomarkers in TETs, aiming also to identify potential therapeutic targets in these tumors [ 19 ]. Aberrant epigenetic alterations seem to be involved in the pathogenesis of thymomas and thymic carcinomas [ 19 ]; however, the possible role epigenetic regulators, such as histone variants, histone modifications and their related chromatin remodelers remains largely unexplored. In this aspect, the present investigation studies for the first time the immunohistochemical expression of histone modification H3K4me3, histone variant CENP-A, as well as chaperones HJURP and DAXX in TETs.…”

“…On the other hand, there has recently been a great interest in the possible usage of immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein-1 or programmed death-ligand 1 (PD-L1) as a therapeutical option for TETs, since they typically exhibit a PDL-1high phenotype [ 17 ]. At the same time, the research of epigenetic alterations in TETs has attracted the interest of medical oncologists and pathologists aiming to search for possible epigenetic biomarkers and to explore possible novel treatment options for these tumors [ 19 ]. In this context, numerous studies have reported the significant role of on non-coding RNA clusters and altered gene methylation in the tumorigenesis of TETs, which seem to be the most common epigenetic alterations in these tumors [ 19 ].…”

“…At the same time, the research of epigenetic alterations in TETs has attracted the interest of medical oncologists and pathologists aiming to search for possible epigenetic biomarkers and to explore possible novel treatment options for these tumors [ 19 ]. In this context, numerous studies have reported the significant role of on non-coding RNA clusters and altered gene methylation in the tumorigenesis of TETs, which seem to be the most common epigenetic alterations in these tumors [ 19 ].…”