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Genome-wide loss of maternal alleles in a nephrogenic rest and Wilms' tumour from a BWS patient

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Abstract

A patient with Beckwith-Wiedemann syndrome (BWS) presented with Wilms' tumour. Examination of the nephrectomy specimen showed, in addition to the tumour, the presence of nephrogenic rests. Nephrogenic rests are thought to be precursor lesions from which a Wilms' tumour may develop. A molecular analysis examining the loss of constitutional heterozygosity (LOCH), initially for chromosome 11, was performed on peripheral blood, the normal kidney, nephrogenic rest and tumour material. The study was extended to include markers from all 23 chromosomes. At each informative, locus, LOCH of the maternal allele was shown in the nephrogenic rest and tumour material. In addition, the normal kidney displayed allele imbalance. It would appear from these results that either extensive LOCH across the genome was an early genetic event in the development of malignancy in this patient or that the tumour and rest developed from cells containing no maternal chromosomes. The apparent LOCH seen in the normal kidney sample implies that full reduction to homozygosity is consistent with a histologically normal appearance. Putative mechanisms to explain this phenomenon are discussed.

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Authors and Affiliations

  1. CRC Department of Cancer Genetics, Paterson Institute of Cancer Research, Christie (CRC) Research Trust, Wilmslow Road, M20 9BX, Manchester, UK

    Paul R. Hoban, Jim Heighway & Gavin R. M. White

  2. Department of Pathology, Giving for Living Research Centre, Royal Manchester Childrens Hospital, Pendlebury, M27 1HA, Manchester, UK

    Paul R. Hoban, Jackie Gardner, Pat Morris-Jones & Anna M. Kelsey

  3. CRC Department of Gene Regulation, Christie (CRC) Research Trust, Wilmslow Road, M20 9BX, Manchester, UK

    Bart Baker

  4. CRC Paediatric and Familial Cancer Research Group, Christie (CRC) Research Trust, Wilmslow Road, M20 9BX, Manchester, UK

    Jill M. Birch

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  1. Paul R. Hoban
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  2. Jim Heighway
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  3. Gavin R. M. White
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  4. Bart Baker
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  5. Jackie Gardner
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  6. Jill M. Birch
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  7. Pat Morris-Jones
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  8. Anna M. Kelsey
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Hoban, P.R., Heighway, J., White, G.R.M. et al. Genome-wide loss of maternal alleles in a nephrogenic rest and Wilms' tumour from a BWS patient. Hum Genet 95, 651–656 (1995). https://doi.org/10.1007/BF00209482

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  • DOI: https://doi.org/10.1007/BF00209482

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