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Distinct epigenetic phenotypes in seminomatous and nonseminomatous testicular germ cell tumors

Oncogene volume 21, pages 3909–3916 (2002)Cite this article

Abstract

The genetic nature of testicular germ cell tumors and the molecular mechanisms underlying the morphological and clinical differences between the two subtypes, seminomas and nonseminomas, remains unclear. Genetic studies show that both subtypes exhibit many of the same regional genomic disruptions, although the frequencies vary and few clear differences are found. We demonstrate significant epigenetic differences between seminomas and nonseminomas by restriction landmark genomic scanning. Seminomas show almost no CpG island methylation, in contrast to nonseminomas that show CpG island methylation at a level similar to other solid tumors. We find an average of 1.11% of CpG islands methylation in nonseminomas, but only 0.08% methylated in seminomas. Furthermore, we demonstrate that seminomas are more highly hypomethylated than nonseminomas throughout their genome. Since both subtypes are thought to arise from primordial germ cells, the epigenetic differences seen between these subtypes may reflect the normal developmental switch in primordial germ cells from an undermethylated genome to a normally methylated genome. We discuss these findings in relation to different developmental models for seminomatous and nonseminomatous testicular germ cell tumors.

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Acknowledgements

We thank Dr Laura Rush for critical reading of the manuscript. We thank Drs Jill James and Igor Pogribny for consultation concerning the cytosine extension assay. We thank Dr Fred Wright and Sandya Liyanarachchi for assistance with statistical analysis. We thank Julia Hall and Yue-Zhong Wu for technical assistance. This work was supported in part by grant P30CA16058, National Cancer Institute, Bethesda, MD, USA. DJ Smiraglia was supported in part by grant T32 CA09338-20, National Cancer Institute, Bethesda, MD, USA. SM Kraggerud and RA Lothe were supported by grants from the Norwegian Cancer Society.

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Authors and Affiliations

  1. Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, 43210, Ohio, OH, USA

    Dominic J Smiraglia, Jadwiga Szymanska, Päivi Peltomäki & Christoph Plass

  2. Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, 0310, Norway

    Sigrid M Kraggerud & Ragnhild A Lothe

  3. Department of Medical Genetics, University of Helsinki, Finland

    Päivi Peltomäki

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  1. Dominic J Smiraglia
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  2. Jadwiga Szymanska
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Correspondence to Dominic J Smiraglia.

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Smiraglia, D., Szymanska, J., Kraggerud, S. et al. Distinct epigenetic phenotypes in seminomatous and nonseminomatous testicular germ cell tumors. Oncogene 21, 3909–3916 (2002). https://doi.org/10.1038/sj.onc.1205488

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