The Role of DNA/Histone Modifying Enzymes and Chromatin Remodeling Complexes in Testicular Germ Cell Tumors

Despite being globally infrequent, testicular germ cell tumors (TGCTs) represent the most common neoplasms in young adult Caucasian men. They are challenging tumors, hallmarked by striking heterogeneity; however, they show very few mutations and share the same (almost) unifying cytogenetic abnormality, in the form of isochromosome 12p. This leaves room for Epigenetic phenomena to explain such diversity. Epigenetic mechanisms frequently deregulated in various cancer types include DNA methylation, non-coding RNAs, but also the effect on chromatin accessibility subsequent to histone post-translational modifications (PTMs) and to the action of chromatin remodeling complexes (ChRCs). These modifications are introduced by complex families of enzymes (DNA and histone modifying enzymes) which show, naturally, deregulated expression in cancer. However, and despite epigenetic (de)regulation being especially relevant in TGCTs, few studies have addressed the role of these enzymes in this tumor model.

In this work, we have reviewed all available papers focused on studying the role of these players in TGCTs. Also, importantly, we used a publicly available database (The Cancer Genome Atlas database, by use of the cBioPortal tool) to inquire about deregulation of expression of these enzymes in a cohort of TGCTs. These in silico tools are publicly available and can help to identify the most relevant players, that could be subsequently pursued and validated in other cohorts.

All in all, we have pointed out the most relevant enzymes in each family, which can help discriminate among tumor entities (namely Seminomas vs Non-Seminomas), dictate prognosis (associating with tumor stage) and even determine survival outcomes. Finally, these players might also be targets of specific therapies, some of which are already available, including HDAC or DNMT inhibitors, which could allow reducing the side effects associated with conventional chemotherapy regimens.

Written by: João Lobo, MD, Resident in Pathology, PhD student, Cancer Biology & Epigenetics Group, Research Center, Portuguese Oncology Institute of Porto (IPO-Porto) & PhD student in Molecular Pathology and Genetics Lecturer in Pathology, Master Degree in Medicine Biomedical Sciences Institute Abel Salazar, University of Porto (ICBAS-UP) & PhD student, Looijenga Group Princess Máxima Center (PMC) for Pediatric Oncology, Utrecht

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