Distinct epigenetic phenotypes in seminomatous and nonseminomatous testicular germ cell tumors

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. Access through your

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BEING VIEWED BY OTHERS GENOMIC LANDSCAPE OF ADULT TESTICULAR GERM CELL TUMOURS IN THE 100,000 GENOMES PROJECT Article Open access 26 October 2024 INTEGRATED GENOMIC ANALYSIS REVEALS

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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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * Department of Genetics, Institute for Cancer

Research, The Norwegian Radium Hospital, Oslo, 0310, Norway Sigrid M Kraggerud & Ragnhild A Lothe * Department of Medical Genetics, University of Helsinki, Finland Päivi Peltomäki

Authors * Dominic J Smiraglia View author publications You can also search for this author inPubMed Google Scholar * Jadwiga Szymanska View author publications You can also search for this

author inPubMed Google Scholar * Sigrid M Kraggerud View author publications You can also search for this author inPubMed Google Scholar * Ragnhild A Lothe View author publications You can

also search for this author inPubMed Google Scholar * Päivi Peltomäki View author publications You can also search for this author inPubMed Google Scholar * Christoph Plass View author

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THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 11 December 2001 * Revised: 14 March 2002 * Accepted: 18 March 2002 * Published: 28 May 2002 *

Issue Date: 30 May 2002 * DOI: https://doi.org/10.1038/sj.onc.1205488 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry,

a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * DNA methylation * nonseminoma

* seminoma * RLGS * genome scan