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

Oncogene volume 22, pages 7695–7701 (2003)Cite this article

Abstract

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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References

  • Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW and Pinkel D . (2000). Nat. Genet., 25, 144–146.

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

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

  • Guan XY, Sham JS, Tang TC, Fang Y, Huo KK and Yang JM . (2001). Cancer Res., 61, 3806–3809.

  • Heidenblad M, Jonson T, Mahlamaki EH, Gorunova L, Karhu R, Johansson B and Hoglund M . (2002). Genes Chromosom. Cancer, 34, 211–223.

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

  • Huntsman DG, Chin SF, Muleris M, Batley SJ, Collins VP, Wiedemann LM, Aparicio S and Caldas C . (1999). Oncogene, 18, 7975–7984.

  • Korn MW, Olde Weghuis DEM, Suijkerbuijk RF, Schmidt U, Otto T, Du Manoir S, Geurts van Kessel A, Seeber S and Becher R . (1996). Genes Chromosom. Cancer, 17, 78–87.

  • Looijenga LHJ and Oosterhuis JW . (2002). Analyt. Quant. Cytol. Histol., 24, 263–279.

  • Looijenga LHJ, Rosenberg C, Van Gurp RJHLM, Geelen E, Van Echten-Arends J, De Jong B, Mostert MC and Oosterhuis JW . (2000). J. Pathol., 19, 187–192.

  • Looijenga LHJ, Stoop H, De Leeuw PJC, De Gouveia Brazao CA, Gillis AJM, Van Roozendaal KEP, Van Zoelen EJJ, Weber RFA, Wolffenbuttel KP, CVan Dekken H, Honecker F, Bokemeyer C, Perlman EJ, Schneider DT, Kononen J, Sauter G and Oosterhuis JW . (2003). Cancer Res., 63, 2244–2250.

  • Monni O, Barlund M, Mousses S, Kononen J, Sauter G, Heiskanen M, Paavola P, Avela K, Chen Y, Bittner ML and Kallioniemi A . (2001). Proc. Natl. Acad. Sci. USA, 1, 1.

  • Mostert MC, Van de Pol M, Olde Weghuis D, Suijkerbuijk RF, Geurts van Kessel A, Van Echten-Arends J, Oosterhuis JW and Looijenga LHJ . (1996). Cancer Genet. Cytogenet., 89, 146–152.

  • Mostert MC, Verkerk AJMH, Van de Pol M, Heighway J, Marynen P, Rosenberg C, Geurts van Kessel A, van Echten J, Oosterhuis JW and Looijenga LHJ . (1998). Oncogene, 16, 2617–2627.

  • Mostofi FK and Sesterhenn IA . (1985). Prog. Clin. Biol. Res., 203, 1–34.

  • Moul JW, Theune SM and Chang EH . (1992). Genes Chromosom. Cancer, 5, 109–118.

  • Mulder MP, Keijzer W, Verkerk A, Boot AJM, Prins MEF, Splinter TAW and Bos JL . (1989). Oncogene, 4, 1345–1351.

  • Nonet GH, Stampfer MR, Chin K, Gray JW, Collins CC and Yaswen P . (2001). Cancer Res., 61, 1250–1254.

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

  • Oosterhuis JW, Castedo SMMJ, De Jong B, Cornelisse CJ, Dam A, Sleijfer DT and Schraffordt Koops H . (1989). Lab. Invest., 60, 14–20.

  • Reiter RE, Sato I, Thomas G, Qian J, Gu Z, Watabe T, Loda M and Jenkins RB . (2000). Genes Chromosom. Cancer, 27, 95–103.

  • Ridanpää M, Lothe RA, nfelt A, Fosså SD, BÆrresen AL and Husgafvel-Pursiainen K . (1993). Environ. Health Perspect., 101, 185–187.

  • Rodriguez S, Jafer O, Goker H, Summersgill BM, Zafarana G, Gillis AJM, Van Gurp RJHLM, Oosterhuis JW, Lu Y-J, Huddart R, Cooper CS, Clark J, Looijenga LHJ and Shipley J . (2003). Oncogene, 22, 1880–1891.

  • Roelofs H, Mostert MC, Pompe K, Zafarana G, Van Oorschot M, Van Gurp RJHLM, Gillis AJM, Stoop H, Rodenhuis S, Oosterhuis JW, Bokemeyer C and Looijenga LJ . (2000). Am. J. Pathol., 157, 1155–1166.

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

  • Sandberg AA, Meloni AM and Suijkerbuijk RF . (1996). J. Urol., 155, 1531–1556.

  • Schmidt BA, Rose A, Steinhoff C, Strohmeyer T, Hartmann M and Ackermann R . (2001). Cancer Res., 61, 4214–4221.

  • Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner H, Park MY, Robker RL, Richards JS, McGinnis LK, Biggers JD, Eppig JJ, Bronson RT, Elledge SJ and Weinberg RA . (1996). Nature, 384, 470–474.

  • 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, Olde Weghuis DEM, Roque L, Forus A, Stellink F, Siepman A, Van de Kaa C, Soares J and Geurts van Kessel A . (1994). Cancer Genet. Cytogenet., 78, 145–152.

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

  • Telenius H, Carter NP, Bebb CE, Nordenskjold M, Ponder BA and Tunnacliffe A . (1992). Genomics, 13, 718–725.

  • Veltman JA, Schoenmakers EF, Eussen BH, Janssen I, Merkx G, van Cleef B, van Ravenswaaij CM, Brunner HG, Smeets D and Geurts van Kessel A . (2002). Am. J. Hum. Genet., 70, 1269–1276.

  • Yasui K, Imoto I, Fukuda Y, Pimkhaokham A, Yang ZQ, Naruto T, Shimada Y, Nakamura Y and Inazawa J . (2001). Genes Chromosom. Cancer, 32, 112–118.

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

  • Zhou H, Kuang J, Zhong L, Kuo W-L, Gray JW, Sahin A, Brinkley BR and Sen S . (1998). Nat. Genet., 20, 189–193.

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Acknowledgements

This work was financially supported by the Dutch Cancer Society (DDHK 98-1685), Interuniversity Poles of attraction program of Belgium, and the EC COST-B19 action ‘Molecular cytogenetics of solid tumors’ (BG).

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Author notes

  1. Gaetano Zafarana and Beata Grygalewicz: These two authors contributed equally to the work

Authors and Affiliations

  1. Pathology/Laboratory for Exp. Patho-Oncology, Erasmus MC-Erasmus University Medical Center/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

    Gaetano Zafarana, Ad J M Gillis, Ruud J H L M van Gurp, Hans Stoop, Jan Wolter Oosterhuis & Leendert H J Looijenga

  2. Center of Human Genetics, University of Leuven, Leuven, Belgium

    Beata Grygalewicz & Maria Debiec-Rychter

  3. Cytogenetic Laboratory, The Maria Sklodowska-Curie Memorial Cancer Center and Institute, Warsaw, Poland

    Beata Grygalewicz

  4. Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands

    Lisenka E L M Vissers, Walter van de Vliet, Ad Geurts van Kessel, Eric F P M Schoenmakers & Joris A Veltman

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  1. Gaetano Zafarana
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Correspondence to Leendert H J Looijenga.

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Zafarana, G., Grygalewicz, B., Gillis, A. et al. 12p-Amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH. Oncogene 22, 7695–7701 (2003). https://doi.org/10.1038/sj.onc.1207011

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