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Gene Review

TGCT1  -  testicular germ cell tumor susceptibility 1

Homo sapiens

 
 
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Disease relevance of TGCT1

 

Psychiatry related information on TGCT1

 

High impact information on TGCT1

  • Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations [2].
  • Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT [2].
  • 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 [6].
  • In the present study the role of the CD95 death pathway in cisplatin sensitivity of TGCT cells was studied in Tera and its in vitro acquired cisplatin-resistant subclone Tera-CP [7].
  • In contrast, CD95L blocking had no effect on cisplatin-induced apoptosis in Tera-CP or Scha, an intrinsic resistant TGCT cell line, nor did anti-CD95 antibody induce additional apoptosis in cisplatin-treated Tera-CP or Scha cells [7].
 

Chemical compound and disease context of TGCT1

 

Biological context of TGCT1

 

Anatomical context of TGCT1

  • In the adult testis, positive immunohistochemistry for OCT3/4 is an absolute indicator for the presence of the TGCT precursor carcinoma in situ/intratubular germ cell neoplasia undifferentiated (CIS/ITGCNU), seminoma, and/or embryonal carcinoma [17].
  • Analyses of two TGCT cell lines indicated that the tumour cells not only express IFNgamma mRNA, but also produce and secrete IFNgamma protein; tumour-derived IFNgamma provokes IP-10 expression and secretion by endothelial cells in vitro, as assessed by PCR and ELISA [18].
  • Chromosome aberrations in 20 lymphocytes of 20 patients with testicular germ cell tumors (TGCT) treated with surgery alone were compared with those of 20 cells from 20 healthy controls using standard G-banding technique [19].
  • CONCLUSIONS: Immunocytological semen analysis based on expression of fetal germ cell markers in exfoliated cells has auxiliary diagnostic value, as it detects some patients with CIS/incipient tumour, but a negative result does not exclude TGCT [20].
  • Despite the large capacity for differentiation displayed by TGCT stem cells, little is known of the factors controlling their developmental potency [21].
 

Associations of TGCT1 with chemical compounds

  • Human TGCT cells were implanted in the left testis of male severe combined immunodeficient mice receiving either no treatment or hormone manipulation treatment [blockade of gonadotropin-releasing hormone secretion and/or signaling using leuprolide or leuprolide plus exogenous testosterone] [22].
  • Previous work has documented activating mutations in the KIT receptor tyrosine kinase in testicular germ-cell tumors (TGCT) [23].
  • Impaired estrogen synthesis and/or signaling may be at least partly responsible for inhibition of TGCT growth in the animal model [22].
  • The International Germ Cell Consensus Classification (IGCCC) of testicular germ cell tumors (TGCT) in 1997 included three serum tumor markers, serum lactate dehydrogenase catalytic concentration (S-LD), serum alpha fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) [24].
  • These findings provide little support to the oestrogen hypothesis, but are consistent with higher levels of testosterones and/or AFP being associated with reduced risk of TGCT; alternatively, lower oestrogen/androgen ratios may be associated with reduced risk [25].
 

Analytical, diagnostic and therapeutic context of TGCT1

References

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  2. Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours. Rapley, E.A., Crockford, G.P., Teare, D., Biggs, P., Seal, S., Barfoot, R., Edwards, S., Hamoudi, R., Heimdal, K., Fossâ, S.D., Tucker, K., Donald, J., Collins, F., Friedlander, M., Hogg, D., Goss, P., Heidenreich, A., Ormiston, W., Daly, P.A., Forman, D., Oliver, T.D., Leahy, M., Huddart, R., Cooper, C.S., Bodmer, J.G., Easton, D.F., Stratton, M.R., Bishop, D.T. Nat. Genet. (2000) [Pubmed]
  3. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Nathanson, K.L., Kanetsky, P.A., Hawes, R., Vaughn, D.J., Letrero, R., Tucker, K., Friedlander, M., Phillips, K.A., Hogg, D., Jewett, M.A., Lohynska, R., Daugaard, G., Richard, S., Chompret, A., Bonaïti-Pellié, C., Heidenreich, A., Olah, E., Geczi, L., Bodrogi, I., Ormiston, W.J., Daly, P.A., Oosterhuis, J.W., Gillis, A.J., Looijenga, L.H., Guilford, P., Fosså, S.D., Heimdal, K., Tjulandin, S.A., Liubchenko, L., Stoll, H., Weber, W., Rudd, M., Huddart, R., Crockford, G.P., Forman, D., Oliver, D.T., Einhorn, L., Weber, B.L., Kramer, J., McMaster, M., Greene, M.H., Pike, M., Cortessis, V., Chen, C., Schwartz, S.M., Bishop, D.T., Easton, D.F., Stratton, M.R., Rapley, E.A. Am. J. Hum. Genet. (2005) [Pubmed]
  4. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. West, R.B., Rubin, B.P., Miller, M.A., Subramanian, S., Kaygusuz, G., Montgomery, K., Zhu, S., Marinelli, R.J., De Luca, A., Downs-Kelly, E., Goldblum, J.R., Corless, C.L., Brown, P.O., Gilks, C.B., Nielsen, T.O., Huntsman, D., van de Rijn, M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors. Looijenga, L.H., de Leeuw, H., van Oorschot, M., van Gurp, R.J., Stoop, H., Gillis, A.J., de Gouveia Brazao, C.A., Weber, R.F., Kirkels, W.J., van Dijk, T., von Lindern, M., Valk, P., Lajos, G., Olah, E., Nesland, J.M., Fosså, S.D., Oosterhuis, J.W. Cancer Res. (2003) [Pubmed]
  6. Differentiation of human embryonal carcinomas in vitro and in vivo reveals expression profiles relevant to normal development. Skotheim, R.I., Lind, G.E., Monni, O., Nesland, J.M., Abeler, V.M., Fosså, S.D., Duale, N., Brunborg, G., Kallioniemi, O., Andrews, P.W., Lothe, R.A. Cancer Res. (2005) [Pubmed]
  7. Loss of drug-induced activation of the CD95 apoptotic pathway in a cisplatin-resistant testicular germ cell tumor cell line. Spierings, D.C., de Vries, E.G., Vellenga, E., de Jong, S. Cell Death Differ. (2003) [Pubmed]
  8. p53 in human embryonal carcinoma: identification of a transferable, transcriptional repression domain in the N-terminal region of p53. Curtin, J.C., Spinella, M.J. Oncogene (2005) [Pubmed]
  9. Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice. Zeiger, M.A., Saji, M., Gusev, Y., Westra, W.H., Takiyama, Y., Dooley, W.C., Kohn, L.D., Levine, M.A. Endocrinology (1997) [Pubmed]
  10. Expression of p53, Bcl-2 and Bax in cisplatin-induced apoptosis in testicular germ cell tumour cell lines. Burger, H., Nooter, K., Boersma, A.W., Kortland, C.J., Stoter, G. Br. J. Cancer (1998) [Pubmed]
  11. Bone morphogenetic proteins and retinoic acid induce human endogenous retrovirus HERV-K expression in NT2D1 human embryonal carcinoma cells. Caricasole, A., Ward-van Oostwaard, D., Mummery, C., van den Eijnden-van Raaij, A. Dev. Growth Differ. (2000) [Pubmed]
  12. The roles of supernumerical X chromosomes and XIST expression in testicular germ cell tumors. Kawakami, T., Okamoto, K., Sugihara, H., Hattori, T., Reeve, A.E., Ogawa, O., Okada, Y. J. Urol. (2003) [Pubmed]
  13. Frequent epigenetic inactivation of the RASSF1A tumour suppressor gene in testicular tumours and distinct methylation profiles of seminoma and nonseminoma testicular germ cell tumours. Honorio, S., Agathanggelou, A., Wernert, N., Rothe, M., Maher, E.R., Latif, F. Oncogene (2003) [Pubmed]
  14. Erasure of methylation imprint at the promoter and CTCF-binding site upstream of H19 in human testicular germ cell tumors of adolescents indicate their fetal germ cell origin. Kawakami, T., Zhang, C., Okada, Y., Okamoto, K. Oncogene (2006) [Pubmed]
  15. Loss of heterozygosity, differentiation, and clonality in microdissected male germ cell tumours. Rothe, M., Albers, P., Wernert, N. J. Pathol. (1999) [Pubmed]
  16. The attractive Achilles heel of germ cell tumours: an inherent sensitivity to apoptosis-inducing stimuli. Spierings, D.C., de Vries, E.G., Vellenga, E., de Jong, S. J. Pathol. (2003) [Pubmed]
  17. Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours. de Jong, J., Stoop, H., Dohle, G.R., Bangma, C.H., Kliffen, M., van Esser, J.W., van den Bent, M., Kros, J.M., Oosterhuis, J.W., Looijenga, L.H. J. Pathol. (2005) [Pubmed]
  18. Expression of CXC chemokine IP-10 in testicular germ cell tumours. Schweyer, S., Soruri, A., Baumhoer, D., Peters, J., Cattaruzza, M., Radzun, H.J., Fayyazi, A. J. Pathol. (2002) [Pubmed]
  19. No evidence for constitutional chromosome instability in testicular cancer. Heimdal, K., Fosså, S.D., Brøgger, A., Møller, P. Hum. Genet. (1992) [Pubmed]
  20. Towards a non-invasive method for early detection of testicular neoplasia in semen samples by identification of fetal germ cell-specific markers. Hoei-Hansen, C.E., Carlsen, E., Jorgensen, N., Leffers, H., Skakkebaek, N.E., Rajpert-De Meyts, E. Hum. Reprod. (2007) [Pubmed]
  21. Bone morphogenetic proteins (BMPs) induce epithelial differentiation of NT2D1 human embryonal carcinoma cells. Caricasole, A., Ward-van Oostwaard, D., Zeinstra, L., van den Eijnden-van Raaij, A., Mummery, C. Int. J. Dev. Biol. (2000) [Pubmed]
  22. Testicular germ cell tumors exhibit evidence of hormone dependence. Douglas, M.L., Richardson, M.M., Nicol, D.L. Int. J. Cancer (2006) [Pubmed]
  23. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults. Bignell, G., Smith, R., Hunter, C., Stephens, P., Davies, H., Greenman, C., Teague, J., Butler, A., Edkins, S., Stevens, C., O'Meara, S., Parker, A., Avis, T., Barthorpe, S., Brackenbury, L., Buck, G., Clements, J., Cole, J., Dicks, E., Edwards, K., Forbes, S., Gorton, M., Gray, K., Halliday, K., Harrison, R., Hills, K., Hinton, J., Jones, D., Kosmidou, V., Laman, R., Lugg, R., Menzies, A., Perry, J., Petty, R., Raine, K., Shepherd, R., Small, A., Solomon, H., Stephens, Y., Tofts, C., Varian, J., Webb, A., West, S., Widaa, S., Yates, A., Gillis, A.J., Stoop, H.J., van Gurp, R.J., Oosterhuis, J.W., Looijenga, L.H., Futreal, P.A., Wooster, R., Stratton, M.R. Genes Chromosomes Cancer (2006) [Pubmed]
  24. Laboratory markers and germ cell tumors. von Eyben, F.E. Critical reviews in clinical laboratory sciences. (2003) [Pubmed]
  25. Maternal hormone levels among populations at high and low risk of testicular germ cell cancer. Zhang, Y., Graubard, B.I., Klebanoff, M.A., Ronckers, C., Stanczyk, F.Z., Longnecker, M.P., McGlynn, K.A. Br. J. Cancer (2005) [Pubmed]
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  27. Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours. Almstrup, K., Hoei-Hansen, C.E., Nielsen, J.E., Wirkner, U., Ansorge, W., Skakkebaek, N.E., Rajpert-De Meyts, E., Leffers, H. Br. J. Cancer (2005) [Pubmed]
  28. Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review. Hoei-Hansen, C.E., Rajpert-De Meyts, E., Daugaard, G., Skakkebaek, N.E. Ann. Oncol. (2005) [Pubmed]
 
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