The epigenome of testicular germ cell tumors |
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Authors: | Lind Guro E Skotheim Rolf I Lothe Ragnhild A |
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Affiliation: | Department of Cancer Prevention, Rikshospitalet - Radiumhospitalet Medical Centre, Montebello and Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway. |
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Abstract: | Gene expression is tightly regulated in normal cells, and epigenetic changes disturbing this regulation are a common mechanism in the development of cancer. Testicular germ cell tumor (TGCT) is the most common malignancy among young males and can be classified into two main histological subgroups: seminomas, which are basically devoid of DNA methylation, and nonseminomas, which in general have methylation levels comparable with other tumor tissues, as shown by restriction landmark genome scanning (RLGS). In general, DNA methylation seems to increase with differentiation, and among the nonseminomas, the pluripotent and undifferentiated embryonal carcinomas harbor the lowest levels of DNA promoter hypermethylation, whereas the well-differentiated teratomas display the highest. In this regard, TGCTs resemble the early embryogenesis. So far, only a limited number of tumor suppressor genes have been shown to be inactivated by DNA promoter hypermethylation in more than a minor percentage of TGCTs, including MGMT, SCGB3A1, RASSF1A, HIC1, and PRSS21. In addition, imprinting defects, DNA hypomethylation of testis/cancer associated genes, and the presence of unmethylated XIST are frequent in TGCTs. Aberrant DNA methylation has the potential to improve current diagnostics by noninvasive testing and might also serve as a prognostic marker for treatment response. |
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Keywords: | Cancer/testis associated genes DNA methylation embryogenesis epigenetics germ cell tumor HIC1 imprinting MGMT PRSS21 RASSF1A SCGB3A1 testicular cancer X chromosome inactivation |
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