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Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma

Oncogene volume 24, pages 6441–6449 (2005)Cite this article

Abstract

The paediatric eye tumour retinoblastoma is initiated by inactivation of RB1, a tumour suppressor on chromosome 13q. In addition to RB1 loss, many retinoblastomas show other genetic alterations including gains on chromosomes 6p21–pter and 1q31–q32. Recently, the minimal region of gains on chromosome 6 was narrowed to band p22. We examined genomic gains and expression changes in primary retinoblastomas to identify potential target genes in 6p22. Quantitative multiplex PCR detected copy numbers ⩾3 in 25 (33%) tumours and no gains in 31 of 76 (40%) tumours. The remaining 20 (26%) samples showed gains only at some loci, most often including E2F3 and DEK in 6p22.3. Analysis of RNA from 21 primary retinoblastomas showed that expression levels of these and some other genes in 6p22 correspond to DNA gains. However, KIF 13A, a reported candidate oncogene on 6p, was expressed at low levels or absent. Clinical manifestation of tumours with gains at all 6p22 loci was distinct in that distribution of age at diagnosis was markedly shifted to older age compared to tumours with no or partial gains. In summary, our results suggest that DEK and E2F3 are potential targets of 6p gains in retinoblastoma.

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Acknowledgements

We thank Claudia Gruss for providing DEK antibody and recombinant HIS-DEK. We thank Kathy Astrahantseff for critical reading of the manuscript. This work was supported by grants from the Deutsche Forschungsgemeinschaft (Klinische Forschergruppe Ophthalmologische Onkologie und Genetik KFO 109, Lo 530/6-1 and Ri 1123/1-1), Nationales Genomforschungsnetz (NGFN), the IFORES program of the Medizinische Fakultät der Universität Duisburg-Essen, and the Kulturstiftung Essen.

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Authors and Affiliations

  1. University Children's Hospital of Essen, Universitätsklinikum Essen, Essen, D-45122, Germany

    Corinna Grasemann, Harald Stephan, Alexander Schramm & Angelika Eggert

  2. Institut für Humangenetik, Universitätsklinikum Essen, Essen, D-45122, Germany

    Sandrine Gratias & Dietmar R Lohmann

  3. Augenklinik, Universitätsklinikum Essen, Essen, D-45122, Germany

    Andreas Schüler

  4. Institut für Zellbiologie, Universitätsklinikum Essen, Virchowstr. 173, Essen, 45122, Germany

    Ludger Klein-Hitpass

  5. Institut fuer Humangenetik und Anthropologie, Universitaetsstraße 1, Universität Düsseldorf, Düsseldorf, D-40225, Germany

    Harald Rieder

  6. Institut für klinische Genetik, Universitätsklinikum Marburg, Marburg, D-35033, Germany

    Stephanie Schneider

  7. Department of Biology, University of Konstanz, Konstanz, D-78457, Germany

    Ferdinand Kappes

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  1. Corinna Grasemann
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Correspondence to Dietmar R Lohmann.

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This work was presented in part at the AACR 95th annual meeting, March 2004

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Grasemann, C., Gratias, S., Stephan, H. et al. Gains and overexpression identify DEK and E2F3 as targets of chromosome 6p gains in retinoblastoma. Oncogene 24, 6441–6449 (2005). https://doi.org/10.1038/sj.onc.1208792

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