Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development

Rolf I. Skotheim, Guro E. Lind, Outi Monni, Jahn M. Nesland, Vera M. Abeler, Sophie D. Fosså, Nur Duale, Gunnar Brunborg, Olli Kallioniemi, Peter W. Andrews, Ragnhild A. Lothe (Corresponding Author)

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Abstract

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.
Original languageEnglish
Pages (from-to)5588-5598
JournalCancer Research
Volume65
Issue number13
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

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Embryonal Carcinoma
Genes
Genomic Imprinting
Seminoma
Homeobox Genes
DNA Methylation
Microarray Analysis
Embryonic Stem Cells
Tumor Biomarkers
In Vitro Techniques
Oligonucleotide Array Sequence Analysis
Transcriptome
Embryonic Development
Testis
Carcinoma
Cell Line

Cite this

Skotheim, R. I., Lind, G. E., Monni, O., Nesland, J. M., Abeler, V. M., Fosså, S. D., ... Lothe, R. A. (2005). Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development. Cancer Research, 65(13), 5588-5598. https://doi.org/10.1158/0008-5472.CAN-05-0153
Skotheim, Rolf I. ; Lind, Guro E. ; Monni, Outi ; Nesland, Jahn M. ; Abeler, Vera M. ; Fosså, Sophie D. ; Duale, Nur ; Brunborg, Gunnar ; Kallioniemi, Olli ; Andrews, Peter W. ; Lothe, Ragnhild A. / Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development. In: Cancer Research. 2005 ; Vol. 65, No. 13. pp. 5588-5598.
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title = "Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development",
abstract = "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.",
author = "Skotheim, {Rolf I.} and Lind, {Guro E.} and Outi Monni and Nesland, {Jahn M.} and Abeler, {Vera M.} and Foss{\aa}, {Sophie D.} and Nur Duale and Gunnar Brunborg and Olli Kallioniemi and Andrews, {Peter W.} and Lothe, {Ragnhild A.}",
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Skotheim, RI, Lind, GE, Monni, O, Nesland, JM, Abeler, VM, Fosså, SD, Duale, N, Brunborg, G, Kallioniemi, O, Andrews, PW & Lothe, RA 2005, 'Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development', Cancer Research, vol. 65, no. 13, pp. 5588-5598. https://doi.org/10.1158/0008-5472.CAN-05-0153

Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development. / Skotheim, Rolf I.; Lind, Guro E.; Monni, Outi; Nesland, Jahn M.; Abeler, Vera M.; Fosså, Sophie D.; Duale, Nur; Brunborg, Gunnar; Kallioniemi, Olli; Andrews, Peter W.; Lothe, Ragnhild A. (Corresponding Author).

In: Cancer Research, Vol. 65, No. 13, 2005, p. 5588-5598.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development

AU - Skotheim, Rolf I.

AU - Lind, Guro E.

AU - Monni, Outi

AU - Nesland, Jahn M.

AU - Abeler, Vera M.

AU - Fosså, Sophie D.

AU - Duale, Nur

AU - Brunborg, Gunnar

AU - Kallioniemi, Olli

AU - Andrews, Peter W.

AU - Lothe, Ragnhild A.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1158/0008-5472.CAN-05-0153

DO - 10.1158/0008-5472.CAN-05-0153

M3 - Article

VL - 65

SP - 5588

EP - 5598

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 13

ER -