Polidy of subtypes of primary germ cell tumors of the stress of the testis: Pathogenetic and clinical relevance

Oosterhuis, J. Wolter; Castedo, Sérgio; Jong, Bauke M. de; Cornelisse, Cees J.; Dam, Anke; Sleijfer, Dirk; Koops, Heimen Schraffordt

doi:10.1016/0165-4608(89)90595-5

Cited by 72 publications

(108 citation statements)

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“…Samples were collected and classi®ed as previously described (Oosterhuis et al, 1989). Samples were processed for total RNA isolation exactly as detailed in Mosselman et al (1996).…”

Section: Tissue Samples and In Situ Hybridisationmentioning

confidence: 99%

Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours

et al. 1998

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We describe the cloning and initial characterization of a novel cDNA from human embryonal carcinoma (EC) cells. This cDNA, which we named human growth di erentiation factor 3 (hGDF3), encodes the homologue of mouse GDF3, a TGFb superfamily member belonging to the Growth/Di erentiation Factors. We have analysed the expression of hGDF3 in human embryonal carcinoma cell lines and in primary testicular germ cell tumours of adolescents and adults (TGCTs). Expression of hGDF3 in human EC cell lines is stem cell-speci®c, is downregulated upon RA-mediated di erentiation and is increased upon culture of the cells in the presence of activin A. In TGCTs, hGDF3 expression is low in seminomas, while expression in non-seminomas is readily detectable and appears to be associated with the EC and yolk sac components in the tumours. We have also mapped the hGDF3 locus to the short arm of human chromosome 12, a region consistently overrepresented in human testicular germ cell tumours. Thus, hGDF3 represents an embryonal carcinoma stem cell-associated marker both in vitro and in vivo.

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“…Samples were collected and classi®ed as previously described (Oosterhuis et al, 1989). Samples were processed for total RNA isolation exactly as detailed in Mosselman et al (1996).…”

Section: Tissue Samples and In Situ Hybridisationmentioning

confidence: 99%

Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours

et al. 1998

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“…One of these portions was snap frozen in liquid nitrogen, while the other portion was fixed in 4% buffered formalin and embedded in paraffin. Tumours were classified according to the recommendations of the World Health Organization (Mostofi et al, 1987), as described previously (Oosterhuis et al, 1989). In this study, nine seminomas, 11 non-seminomas and two spermatocytic seminomas were included.…”

Section: Tumour Materials and Rna Isolationmentioning

confidence: 99%

Human testicular germ cell tumours express inhibin subunits, activin receptors and follistatin mRNAs

Schaik

Wierikx²,

Looijenga³

et al. 1997

Br J Cancer

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Summary Germ cell development is influenced by activin and inhibin, which are produced by Sertoli cells. Activin also affects differentiation of mouse embryonal carcinoma cells, which, to a certain extent, resemble the embryonal carcinoma component of germ cell tumours. Therefore, the expression of inhibin/activin subunits, of activin receptors and of the activin-binding protein follistatin was studied in testicular germ cell tumours, using RNAase protection assays. Testicular germ cell tumours of adolescents and adults (TGCTs) and spermatocytic seminomas expressed activin type and type 11 receptors (ActRi and ActRII respectively). Seminomas expressed significantly lower levels of ActRIIA (P<0.05, Mann-Whitney U-test) and higher levels of ActRIA (P<0.05) and ActRIB (P<0.05) compared with non-seminomas. All tumours expressed inhibin n-subunit transcripts, which are a prerequisite for activin synthesis. Non-seminomas contained significantly higher levels of the inhibin PA subunit (P<0.001) compared with seminomas. No activin PC subunit transcripts could be demonstrated by RNAase protection. Inhibin a-subunit expression was absent in the spermatocytic seminomas, in six out of nine seminomas and in 10 out of 11 nonseminomas. Follistatin was expressed predominantly in non-seminomas and spermatocytic seminomas. This expression of activin type and type 11 receptors in combination with expression of inhibin 5-subunits indicates that activin may act as a para-or autocrine factor in the regulation of growth and differentiation of tumours of human germ cells.

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“…Representative parts of the tumor were snap frozen in liquid nitrogen, or were fixed in 10% formalin for paraffin embedding. Diagnosis was carried out according to the World Health Organization classification (Mostofi and Sesterhenn, 1985), as described previously (Oosterhuis et al, 1989), supported by immunohistochemistry using antibodies directed against germ cell-specific alkaline phosphatase (PLAP), alpha-feto protein (AFP), human chorionic gonadotropin (HCG), and the stem cell factor receptor c-KIT. In addition, immunohistochemistry for OCT3/4 (POU5F1) was applied, as described before .…”

Section: Sample Handling and Characterizationmentioning

confidence: 99%

12p-Amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH

et al. 2003

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All invasive testicular germ cell tumors of adolescents and adults (TGCTs), that is, seminomas and nonseminomas, show gain of 12p sequences, mostly as isochromosomes. Although several candidate genes have been suggested, the relevant gene(s) have not been identified yet. About 10% of testicular seminomas, however, show a more restricted amplification of the 12p11.2-p12.1 region, in which the various amplicons show an apparent overlap, allowing for the shortest region of amplification overlap approach, aiming at the identification of pathogenetically relevant sequences residing in this region. Here we report on a high-resolution 12p-amplicon architecture analysis using microarray-based comparative genomic hybridization, the results of which were subsequently confirmed by fluorescent in situ hybridization studies. The 12p-specific microarray contained 63 positionally selected BAC clones, which are more or less evenly distributed over the short arm of chromosome 12 (average spacing: less than 500 Kb), including 20 clones within the region of amplification. Out of a series of 17 seminomas, seven seminomas showed amplification of the whole amplicon region, of which three showed a dip in T/R value in the center of the amplified area. A more complex amplification pattern was found in the other 10 seminomas: three showed predominant amplification at the centromeric border; one mainly at the telomeric border; six showed a balanced amplification of both the centromeric and telomeric regions. The only nonseminoma investigated showed a structure in which the centromeric border was only amplified. These data support a mechanistic model in which at least two 12p genes, situated at the border regions of the amplicon, are positional candidates capable of actively supporting tumor progression in TGCTs.

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Polidy of subtypes of primary germ cell tumors of the stress of the testis: Pathogenetic and clinical relevance

Cited by 72 publications

References 0 publications

Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours

Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours

Human testicular germ cell tumours express inhibin subunits, activin receptors and follistatin mRNAs

12p-Amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH

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