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Review
. 2019 Jan 10;20(2):258.
doi: 10.3390/ijms20020258.

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

João Lobo  1   2   3 , Ad J M Gillis  4   5 , Carmen Jerónimo  6   7 , Rui Henrique  8   9   10 , Leendert H J Looijenga  11   12
Affiliations
Review

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

João Lobo et al. Int J Mol Sci. .

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.

Keywords: biomarkers; development; epigenetics; germ cell cancer; methylation; microRNAs; testicular cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cycle of genomic imprinting and global methylation.
Figure 2
Figure 2
Pathogenesis of type II testicular germ cell tumors. Abbreviations: CH—choriocarcinoma; EC—embryonal carcinoma; GCNIS—germ cell neoplasia in situ; SE—seminoma; TE—teratoma; YST—yolk sac tumor.
Figure 3
Figure 3
Chronological view of most relevant publications regarding microRNAs in testicular germ cell tumors (see text for details).
Figure 4
Figure 4
Integrative view of the genvironmental model, with focus on genetic, cytogenetic, and epigenetic factors, which are continuously modified and conditioned by the surrounding environment, ultimately determining the cell fate and tumor progression (see text for details).
See this image and copyright information in PMC

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