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Int. J. Mol. Sci. 2019, 20(2), 258; https://doi.org/10.3390/ijms20020258

Human Germ Cell Tumors are Developmental Cancers: Impact of Epigenetics on Pathobiology and Clinic

1
Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
2
Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
3
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal;
4
Laboratory of Experimental Patho-Oncology (LEPO), Josephine Nefkens Building, Erasmus MC, Department of Pathology, University Medical Center, Cancer Institute, Be-432A, PO Box 2040, 3000 CA Rotterdam, The Netherlands
5
Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Received: 7 December 2018 / Revised: 25 December 2018 / Accepted: 7 January 2019 / Published: 10 January 2019
(This article belongs to the Special Issue Epigenetics of Urological Cancers)
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Abstract

Current (high throughput omics-based) data support the model that human (malignant) germ cell tumors are not initiated by somatic mutations, but, instead through a defined locked epigenetic status, representative of their cell of origin. This elegantly explains the role of both genetic susceptibility as well as environmental factors in the pathogenesis, referred to as ‘genvironment’. Moreover, it could also explain various epidemiological findings, including the rising incidence of this type of cancer in Western societies. In addition, it allows for identification of clinically relevant and informative biomarkers both for diagnosis and follow-up of individual patients. The current status of these findings will be discussed, including the use of high throughput DNA methylation profiling for determination of differentially methylated regions (DMRs) as well as chromosomal copy number variation (CNV). Finally, the potential value of methylation-specific tumor DNA fragments (i.e., XIST promotor) as well as embryonic microRNAs as molecular biomarkers for cancer detection in liquid biopsies will be presented. View Full-Text
Keywords: biomarkers; development; epigenetics; germ cell cancer; methylation; microRNAs; testicular cancer biomarkers; development; epigenetics; germ cell cancer; methylation; microRNAs; testicular cancer
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Lobo, J.; Gillis, A.J.M.; Jerónimo, C.; Henrique, R.; Looijenga, L.H.J. Human Germ Cell Tumors are Developmental Cancers: Impact of Epigenetics on Pathobiology and Clinic. Int. J. Mol. Sci. 2019, 20, 258.

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