This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Skotheim, R. I. Articles by Lothe, R. A. Search for Related Content PubMed PubMed Citation Articles by Skotheim, R. I. Articles by Lothe, R. A.

Differentiation of Human Embryonal Carcinomas In vitro and In vivo Reveals Expression Profiles Relevant to Normal Development

¹ Department of Genetics, Institute for Cancer Research and Departments of ² Pathology and ³ Medical Oncology and Radiotherapy, The Norwegian Radium Hospital and University of Oslo; ⁴ Department of Chemical Toxicology, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway; ⁵ Biomedicum Biochip Center, Biomedicum, University of Helsinki, Helsinki, Finland; ⁶ Medical Biotechnology Group, VTT Technical Research Centre of Finland and University of Turku, Turku, Finland; and ⁷ Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom

Requests for reprints: Ragnhild A. Lothe, Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 Oslo, Norway. Phone: 47-22934415; Fax: 47-22934440; E-mail: rlothe{at}radium.uio.no.

Embryonal carcinoma is a histologic subgroup of testicular germ cell tumors (TGCTs), and its cells may follow differentiation lineages in a manner similar to early embryogenesis. To acquire new knowledge about the transcriptional programs operating in this tumor development model, we used 22k oligo DNA microarrays to analyze normal and neoplastic tissue samples from human testis. Additionally, retinoic acid–induced in vitro differentiation was studied in relevant cell lines. We identified genes characterizing each of the known histologic subtypes, adding up to a total set of 687 differentially expressed genes. Among these, there was a significant overrepresentation of gene categories, such as genomic imprinting and gene transcripts associated to embryonic stem cells. Selection for genes highly expressed in the undifferentiated embryonal carcinomas resulted in the identification of 58 genes, including pluripotency markers, such as the homeobox genes NANOG and POU5F1 (OCT3/4), as well as GAL, DPPA4, and NALP7. Interestingly, abundant expression of several of the pluripotency genes was also detected in precursor lesions and seminomas. By use of tissue microarrays containing 510 clinical testicular samples, GAL and POU5F1 were up-regulated in TGCT also at the protein level and hence validated as diagnostic markers for undifferentiated tumor cells. The present study shows the unique gene expression profiles of each histologic subtype of TGCT from which we have identified deregulated components in selected processes operating in normal development, such as WNT signaling and DNA methylation.

This article has been cited by other articles:

				C. Lalancette, C. Thibault, I. Bachand, N. Caron, and N. Bissonnette Transcriptome Analysis of Bull Semen with Extreme Nonreturn Rate: Use of Suppression-Subtractive Hybridization to Identify Functional Markers for Fertility Biol Reprod, April 1, 2008; 78(4): 618 - 635. [Abstract] [Full Text] [PDF]

				K. Y. Kim, M. K. Kee, S. A. Chong, and M. J. Nam Galanin Is Up-Regulated in Colon Adenocarcinoma Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2373 - 2378. [Abstract] [Full Text] [PDF]

				E. Rajpert-De Meyts Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects Hum. Reprod. Update, May 1, 2006; 12(3): 303 - 323. [Abstract] [Full Text] [PDF]

				J. E. Korkola, J. Houldsworth, R. S.V. Chadalavada, A. B. Olshen, D. Dobrzynski, V. E. Reuter, G. J. Bosl, and R.S.K. Chaganti Down-Regulation of Stem Cell Genes, Including Those in a 200-kb Gene Cluster at 12p13.31, Is Associated with In vivo Differentiation of Human Male Germ Cell Tumors Cancer Res., January 15, 2006; 66(2): 820 - 827. [Abstract] [Full Text] [PDF]