Association Between RASSF1A Promoter Methylation and Testicular Germ Cell Tumor: A Meta-analysis and a Cohort Study

Markulin, Dora; Vojta, Aleksandar; Samaržija, Ivana; Gamulin, Marija; Bečeheli, Ivona; Jukić, Irena; Maglov, Čedomir; Zoldoš, Vlatka; Fučić, Aleksandra

doi:10.21873/cgp.20046

Cited by 11 publications

(9 citation statements)

References 58 publications

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“…The field of Epigenetics in TGCTs has been expanding in the last years, with a growing number of publications on the topic. Most studies have focused on methylation [26,27,28,29] and on microRNAs (miRs) [30,31,32,33], where the major breakthroughs in TGCTs have taken place. Protein-coding epigenetic players, including DNA-modifying enzymes, histone-modifying enzymes, and ChRCs, have been explored in diverse tumor models in the recent years; however, little attention has been paid to TGCTs.…”

Section: Protein-coding Epigenetic Players In Testicular Germ Cellmentioning

confidence: 99%

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

Lobo

Henrique

Jerónimo

2018

Cancers

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It is well established that cancer cells exhibit alterations in chromatin structure and accessibility. Indeed, the dysregulation of many protein-coding players with enzymatic activity (DNA and histone-modifying enzymes) and chromatin remodelers have been depicted in various tumor models in recent years. Still, little attention has been directed towards testicular germ cell tumors (TGCTs)—representing the most common neoplasm among young adult Caucasian men—with most studies focusing on exploring the role of DNA methyltransferases (DNMTs) and DNA demethylases (TETs). TGCTs represent a complex tumor model, associated with developmental and embryogenesis-related phenomena, and display seldom (cyto)genetic aberrations, leaving room for Epigenetics to explain such morphological and clinical diversity. Herein, we have summarized the major findings that were reported in literature regarding the dysregulation of DNA/histone-modifying enzymes and chromatin remodelers in TGCTs. Additionally, we performed in silico analysis of The Cancer Genome Atlas database to find the most relevant of those players in TGCTs. We concluded that several DNA/histone-modifying enzymes and chromatin remodelers may serve as biomarkers for subtyping, dictating prognosis and survival, and, possibly, for serving as targets of directed, less toxic therapies.

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Section: Protein-coding Epigenetic Players In Testicular Germ Cellmentioning

confidence: 99%

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

Lobo

Henrique

Jerónimo

2018

Cancers

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“…In TGCT, downregulated tumor suppressor gene RASSF1A increases proliferation [ 110 , 215 ]. TGCT also has a downregulated RB1 [ 216 ].…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis

Eyben¹,

Kristiansen

Kapp

et al. 2023

IJMS

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In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/POU5F1, SOX17, KLF4, and MYC, and embryonal carcinoma (EC) has four upregulated genes, OCT4/POU5F1, SOX2, LIN28, and NANOG. The EC panel can reprogram cells into iPSC, and both iPSC and EC can differentiate into teratoma. This review summarizes the literature on epigenetic regulation of the genes. Epigenetic mechanisms, such as methylations of cytosines on the DNA string and methylations and acetylations of histone 3 lysines, regulate expression of these driver genes between the TGCT subtypes. In TGCT, the driver genes contribute to well-known clinical characteristics and the driver genes are also important for aggressive subtypes of many other malignancies. In conclusion, epigenetic regulation of the driver genes are important for TGCT and for oncology in general.

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“…It has been assumed that RASSF1 inactivation may be among the first events of TGCT tumorigenesis [58]. PRSS21 is assumed to act as a tumor suppressor gene whose inactivation plays an essential role in TGCT development [6].…”

Section: Healthy Controlsmentioning

confidence: 99%

Testicular Germ Cell Tumor Tissue Biomarker Analysis: A Comparison of Human Protein Atlas and Individual Testicular Germ Cell Tumor Component Immunohistochemistry

Krasic,

Skara Abramovic,

Himelreich Peric

et al. 2023

Cells

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The accurate management of testicular germ cell tumors (TGCTs) depends on identifying the individual histological tumor components. Currently available data on protein expression in TGCTs are limited. The human protein atlas (HPA) is a comprehensive resource presenting the expression and localization of proteins across tissue types and diseases. In this study, we have compared the data from the HPA with our in-house immunohistochemistry on core TGCT diagnostic genes to test reliability and potential biomarker genes. We have compared the protein expression of 15 genes in TGCT patients and non-neoplastic testicles with the data from the HPA. Protein expression was converted into diagnostic positivity. Our study discovered discrepancies in three of the six core TGCT diagnostic genes, POU5F1, KIT and SOX17 in HPA. DPPA3, CALCA and TDGF1 were presented as potential novel TGCT biomarkers. MGMT was confirmed while RASSF1 and PRSS21 were identified as biomarkers of healthy testicular tissue. Finally, SALL4, SOX17, RASSF1 and PRSS21 dysregulation in the surrounding testicular tissue with complete preserved spermatogenesis of TGCT patients was detected, a potential early sign of neoplastic transformation. We highlight the importance of a multidisciplinary collaborative approach to fully understand the protein landscape of human testis and its pathologies.

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Association Between RASSF1A Promoter Methylation and Testicular Germ Cell Tumor: A Meta-analysis and a Cohort Study

Cited by 11 publications

References 58 publications

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

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

Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis

Testicular Germ Cell Tumor Tissue Biomarker Analysis: A Comparison of Human Protein Atlas and Individual Testicular Germ Cell Tumor Component Immunohistochemistry

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