Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Oncogenomics
  • Published:

Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2–p12.1

Abstract

Gain of 12p material is invariably associated with testicular germ cell tumors (TGCTs) of adolescents and adults, most usually as an isochromosome 12p. We analyzed TGCTs with i(12p) using a global approach to expression profiling targeting chromosomes (comparative expressed sequence hybridization, CESH). This indicated overexpression of genes from 12p11.2–p12.1 relative to testis tissue and fibroblasts. The nonseminoma subtype showed higher levels of expression than seminomas. Notably, 12p11.2–p12.1 is amplified in about 10% of TGCTs and CESH analysis of such amplicon cases showed high levels of overexpression from this region. Microarray analysis, including cDNA clones representing most UniGene clusters from 12p11.2–p12.1, was applied to DNA and RNA from 5 TGCTs with amplification of 12p11.2–p12.1 and seven TGCTs with gain of the entire short arm of chromosome 12. Expression profiles were consistent with the CESH data and overexpression of EST595078, MRPS35 and LDHB at 12p11.2–p12.1 was detected in most TGCTs. High-level overexpression of BCAT1 was specific to nonseminomas and overexpression of genes such as CMAS, EKI1, KRAS2, SURB7 and various ESTs correlated with their amplification. Genes such as CCND2, GLU3, LRP6 and HPH1 at 12p13 were also overexpressed. The overexpressed sequences identified, particularly those in the region amplified, represent candidate genes for involvement in TGCT development.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Atkin NB and Baker MC . (1982). Lancet, 2, 1349.

  • Baldini A, Rocchi M, Archidiacono N, Miller OJ, and Miller DA . (1990). Am. J. Hum Genet., 46, 784–788.

  • Ben-Yosef T, Yanuka O, Halle D and Benvenisty N . (1998). Oncogene, 17, 165–171.

  • Benvenisty N, Leder A, Kuo A and Leder P . (1992). Genes Dev., 6, 2513–2523.

  • Bosl GJ and Motzer RJ . (1997). N. Engl. J. Med., 337, 242–253.

  • Bourdon V, Naef F, Rao PH, Reuter V, Mok VS, Bosl G, Koul S, Murty VVVS, Kucherlapati RS and Chaganti RSK . (2002). Cancer Res., 62, 6218–6223.

  • Clark J, Edwards S, John M, Flohr P, Gordon T, Maillard K, Giddings I, Brown C, Bagherzadeh A, Campbell C, Shipley J, Wooster R and Cooper CS . (2002). Genes Chromosomes Cancer, 34, 104–114.

  • Cleveland WS . (1979). J. Am. Stat. Assoc., 74, 829–836.

  • Hayes DF and Thor AD . (2002). Semin. Oncol., 29, 231–245.

  • Hinoi E, Fujimori S, Takemori A and Yoneda Y . (2002). Biochem. Biophys. Res. Commun., 294, 1177–1183.

  • Houldsworth J, Reuter V, Bosl GJ and Chaganti RS . (1997). Cell Growth Differ., 8, 293–299.

  • Kinzler KW, Signer SH, Bigner DD, Trent JM, Law ML, O'Brien SJ, Wong AJ and Vogelstein B . (1987). Science, 236, 70–73.

  • Korn WM, Olde Weghuis DE, Suijkerbuijk RK, Schmidt U, Otto T, du Manoir S, Geurts van Kessel A, Harstrick A, Seeber S and Becher R . (1996). Genes Chromosomes Cancer, 17, 78–87.

  • Lu YJ, Williamson D, Clark J, Wang R, Tiffin N, Skelton L, Gordon T, Williams R, Allan B, Jackman A, Cooper C, Pritchard-Jones K and Shipley J . (2001). Proc. Natl. Acad. Sci. USA, 98, 9197–9202.

  • Mostert MM, van de Pol M, Olde WD, Suijkerbuijk RF, Geurts vK, van Echten J, Oosterhuis JW and Looijenga LH . (1996). Cancer Genet. Cytogenet., 89, 146–152.

  • Olie RA, Fenderson B, Daley K, Oosterhuis JW, Murphy J and Looijenga LH . (1996). Br. J. Cancer, 74, 133–140.

  • Olie RA, Looijenga LH, Boerrigter L, Top B, Rodenhuis S, Langeveld A, Mulder MP and Oosterhuis JW . (1995). Genes Chromosomes Cancer, 12, 110–116.

  • Oosterhuis JW, Castedo SM, de Jong B, Cornelisse CJ, Dam A, Sleijfer DT and Schraffordt KH . (1989). Lab. Invest., 60, 14–21.

  • Pinson KI, Brennan J, Monkley S, Avery BJ and Skarnes WC . (2000). Nature, 407, 535–538.

  • Pollack JR, Perou CM, Alizadeh AA, Eisen MB, Pergamenschikov A, Williams CF, Jeffrey SS, Botstein D and Brown PO . (1999). Nat. Genet., 23, 41–46.

  • Rao PH, Houldsworth J, Palanisamy N, Murty VV, Reuter VE, Motzer RJ, Bosl GJ and Chaganti RS . (1998). Cancer Res., 58, 4260–4263.

  • Roelofs H, Mostert MC, Pompe K, Zafarana G, van Oorschot M, Van Gurp RJ, Gillis AJ, Stoop H, Beverloo B, Oosterhuis JW, Bokemeyer C and Looijenga LH . (2000). Am. J. Pathol., 157, 1155–1166.

  • Rorth M, Rajpert-De Meyts E, Andersson L, Dieckmann KP, Fossa SD, Grigor KM, Hendry WF, Herr HW, Looijenga LH, Oosterhuis JW and Skakkebaek NE . (2000). Scand. J. Urol. Nephrol. Suppl., 205, 166–186.

  • Rosenberg C, Van Gurp RJ, Geelen E, Oosterhuis JW and Looijenga LH . (2000). Oncogene, 19, 5858–5862.

  • Sambrook J and Russell W . Molecular Cloning, A Laboratory Manual. (2001). 3. Cold Spring Harbor Laboratory Press: New York.

    Google Scholar 

  • Skotheim RI, Monni O, Mousses S, Fossa SD, Kallioniemi OP, Lothe RA and Kallioniemi A . (2002). Cancer Res., 62, 2359–2364.

  • Suijkerbuijk RF, Sinke RJ, Meloni AM, Parrington JM, van Echten J, de Jong B, Oosterhuis JW, Sandberg AA and Geurts van Kessel A . (1993) Cancer Genet. Cytogenet., 70, 85–93.

  • Summersgill BM, Jafer O, Wang R, Goker H, Niculescu-Duvaz I, Huddart R and Shipley J . (2001b). Cancer Genet. Cytogenet., 128, 120–129.

  • Summersgill B, Goker H, Osin P, Huddart R, Horwich A, Fisher C and Shipley J . (1998a). Diagn. Mol. Pathol., 7, 260–266.

  • Summersgill B, Goker H, Weber-Hall S, Huddart R, Horwich A and Shipley J . (1998b). Br. J. Cancer, 77, 305–315.

  • Summersgill B, Osin P, Lu YJ, Huddart R and Shipley J . (2001a). Br. J. Cancer, 85, 213–220.

  • von Eyben FE, Liu FJ, Amato RJ and Fritsche HA . (2000). Acta Oncol., 39, 509–517.

  • Windstetter D, Schaefer F, Scharer K, Reiter K, Eife R, Harms HK, Bertele-Harms R, Fiedler F, Tsui LC, Reitmeir P, Horster M and Hadorn HB . (1997). Eur. J. Med. Res., 2, 431–436.

  • Zafarana G, Gillis AJ, Van Gurp RJ, Olsson PG, Elstrodt F, Stoop H, Millan JL, Oosterhuis JW and Looijenga LH . (2002). Cancer Res., 62, 1822–1831.

Download references

Acknowledgements

This work was supported by Cancer Research UK and the Dutch Cancer Society (Grant 98-1685).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J M Shipley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rodriguez, S., Jafer, O., Goker, H. et al. Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2–p12.1. Oncogene 22, 1880–1891 (2003). https://doi.org/10.1038/sj.onc.1206302

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206302

Keywords

This article is cited by

Search

Quick links