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The genomic structure of the DMBT1 gene: evidence for a region with susceptibility to genomic instability

Oncogene volume 18, pages 6233–6240 (1999)Cite this article

Abstract

Increasing evidence has accumulated for an involvement of the inactivation of tumour suppressor genes at chromosome 10q in the carcinogenesis of brain tumours, melanomas, and carcinomas of the lung, the prostate, the pancreas, and the endometrium. The gene DMBT1 (Deleted in Malignant Brain Tumours 1) is located at chromosome 10q25.3 – q26.1, within one of the putative intervals for tumour suppressor genes. DMBT1 is a member of the scavenger-receptor cysteine-rich (SRCR) superfamily and displays homozygous deletions or lack of expression in glioblastoma multiforme, medulloblastoma, and in gastrointestinal and lung cancers. Based on these properties, DMBT1 has been proposed to be a candidate tumour suppressor gene. We have determined the genomic sequence of DMBT1 to allow analyses of mutations. The gene has at least 54 exons that span a genomic region of about 80 kb. We have identified a putative exon with coding potential for a transmembrane domain. Our data further suggest that alternative splicing gives rise to isoforms of DMBT1 with a differential utilization of SRCR domains and SRCR interspersed domains. The major part of the gene harbours locus specific repeats. These repeats may point to the DMBT1 locus as a region susceptible to chromosomal instability.

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Acknowledgements

We appreciate the skillful assistance of Edda Dittert, Alexandra Ochs, Sara Burmester, and Lars Vitved, and we thank Dr Sabine Klauck for support. The work was supported by the Deutsche Krebshilfe grant 10-1260-Po2, the Danish Medical Research Council and the Benzon Foundation.

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Authors and Affiliations

  1. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    J Mollenhauer, S Wiemann, I Krebs, S Herbertz, P Kioschis, J F Coy & A Poustka

  2. Immunology and Microbiology, Institute for Medical Biology, University of Southern Denmark, Odense University, Winsløwparken 19, Odense, 5000, C, Denmark

    U Holmskov & J Madsen

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  1. J Mollenhauer
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Mollenhauer, J., Holmskov, U., Wiemann, S. et al. The genomic structure of the DMBT1 gene: evidence for a region with susceptibility to genomic instability. Oncogene 18, 6233–6240 (1999). https://doi.org/10.1038/sj.onc.1203071

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