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.
Highlights
Germ Cell Tumors in GeneralA number of different cell types can be found in the testis; and despite being a relatively small organ, the testis may give rise to a large variety of neoplasms
More than 95% of testicular neoplasms are derived from germ cells arrested in their differentiation—the testicular germ cell tumors (TGCTs) [1]—meaning that global epidemiological trends for testicular cancer mostly refer to this group of neoplasms
Germ cell tumors (GCTs) are not a single class of neoplasms; instead, they represent a heterogeneous array of tumor entities, arising either in the gonads or being extragonadal, reflecting a complex and development-related tumor model, each subclass showing its peculiarities and specific epidemiology
Summary
Germ Cell Tumors in GeneralA number of different cell types can be found in the testis (germ cells, Sertoli cells, Leydig cells, mesenchymal cells, mesothelial cells, among others); and despite being a relatively small organ, the testis may give rise to a large variety of neoplasms. Germ cell tumors (GCTs) are not a single class of neoplasms; instead, they represent a heterogeneous array of tumor entities, arising either in the gonads (both male and female) or being extragonadal (developing from germ cells arrested in their migration along the midline of the body), reflecting a complex and development-related tumor model, each subclass showing its peculiarities and specific epidemiology. The European Cancer Registry-Based Study on Survival and Care of Cancer Patients (EUROCARE) reports markedly distinct age-adjusted incidence rates of GCTs in Europe for males and females (64 per 1,000,000 versus 4 per 1,000,000, respectively) [2]; besides these global differences in incidence, there are histological divergences among testicular and ovarian neoplasms: in males most tumors are seminomas (SEs) and most non-seminomatous tumors (NSTs) are mixed forms, while in women most tumors are NSTs and mixed forms are the exception. Five-year survival is better for gonadal GCTs when compared to extragonadal GCTs [2]
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