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Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours

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Summary

In this paper we describe the analysis of genetic changes in chromosome 11 in Wilms' tumours. Using a range of probes for regions 11p15, 11p13 and 11q we have screened DNA from 14 Wilms' tumours together with control DNA obtained from the patients' lymphocytes and their parents. We have been able to demonstrate loss of heterozygosity in 5 of the 14 different Wilms' tumours. In three of these five tumours, loss of heterozygosity did not involve markers for 11p13, 11p15.4 or the proximal region of 11p15.5, but only some markers assigned to the most distal part of 11p15.5. In two of these tumours we could demonstrate unequal mitotic recombination in 11p with breakpoints in the hypervariable regions 5′ of the insulin gene and/or 3′ of the HRASI protooncogene. In one tumour, from a Beckwith-Wiedemann patient, all markers for the region 11a13-pter became hemizygous; the region 11q13-qter remained heterozygous. These results demonstrate that loss of heterozygosity in Wilms' tumours may not necessarily involve the proposed Wilms' tumour locus at 11p13 but may be limited to 11p15.5. This suggests that not only the 11p13 region, but also the 11p15.5 region is involved in Wilms' tumour development. The possible role of both regions in the development of Wilms' tumour is discussed.

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Authors and Affiliations

  1. Institute of Human Genetics, University of Amsterdam, Academic Medical Centre, Meibergdreef 15, NL-1105 AZ, Amsterdam ZO, The Netherlands

    M. Mannens, R. M. Slater, C. Heyting & J. Bliek

  2. Emma kinderziekenhuis, Spinozastraat 51, NL-1018 HJ, Amsterdam, The Netherlands

    J. de Kraker

  3. Birmingham Children's Hospital, Ladywood Middleway, B16 8ET, Birmingham, UK

    N. Coad

  4. Laboratory for Physiological Chemistry, State University of Utrecht, Vondellaan 24a, NL-3521 GG, Utrecht, The Netherlands

    P. de Pagter-Holthuizen

  5. Department of Human Genetics, State University of Leiden, Wassenaarseweg 72, NL-2333 AL, Leiden, The Netherlands

    P. L. Pearson

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  1. M. Mannens
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  2. R. M. Slater
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  3. C. Heyting
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Mannens, M., Slater, R.M., Heyting, C. et al. Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours. Hum Genet 81, 41–48 (1988). https://doi.org/10.1007/BF00283727

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