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  • Oncogenomics
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Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2

Oncogene volume 22, pages 2343–2351 (2003)Cite this article

Abstract

Deletion of a part of the short arm of chromosome 1 is one of the most common chromosomal rearrangements observed in neuroblastoma (NBL) tumors and it is associated with a poor prognosis. No NBL tumor suppressor gene has yet been identified in the region. Our shortest region of overlap of deletions, ranging from marker D1S80 to D1S244, was shown to partly overlap a 500 kb region that was homozygously deleted in a NBL cell line. We have screened seven genes known to reside in or very close to this overlap consensus region, UBE4B/UFD2, KIF1B, DFFA, PGD, CORT, PEX14, and ICAT, for coding mutations in NBL tumor DNA. A few deviations from the reference sequences were identified; most interestingly being a splice site mutation that was detected in UBE4B/UFD2 in a stage 3 NBL with a fatal outcome. This mutation was neither present in the patients constitutional DNA nor in any of 192 control chromosomes analysed. Also, the expression of UBE4B/UFD2 was markedly diminished in the high-stage/poor-outcome tumors as compared to the low-stage/favorable-outcome tumors. Overall, the number of amino-acid changes in the genes of the region was low, which shows that mutations in these genes are rare events in NBL development. Given the data presented here, UBE4B/UFD2 stands out as the strongest candidate NBL tumor suppressor gene in the region at this stage.

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Acknowledgements

We gratefully acknowledge the financial support of the Swedish Cancer Society, the Children's Cancer Foundation, the IngaBritt and Arne Lundberg Foundation, the Assar Gabrielsson Foundation, the Wilhelm and Martina Lundgren Science Foundation and the Sahlgrenska University Hospital Foundation.

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Authors and Affiliations

  1. Department of Clinical Genetics, Institute for the Health of Women and Children, Göteborg University, Sahlgrenska University Hospital-East, Göteborg, SE-41685, Sweden

    Cecilia Krona, Katarina Ejeskär, Frida Abel, Jill Bjelke, Elin Björk, Rose-Marie Sjöberg & Tommy Martinsson

  2. Cell and Gene Therapy Group, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, 3052, Vic., Australia

    Katarina Ejeskär

  3. Childhood Cancer Research Unit, Karolinska Institute, Karolinska Hospital, Stockholm, SE-17176, Sweden

    Per Kogner

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  1. Cecilia Krona
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Correspondence to Tommy Martinsson.

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Krona, C., Ejeskär, K., Abel, F. et al. Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2. Oncogene 22, 2343–2351 (2003). https://doi.org/10.1038/sj.onc.1206324

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