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  • Oncogenomics
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Characterization of a 500 kb region on 17q25 and the exclusion of candidate genes as the familial Tylosis Oesophageal Cancer (TOC) locus

Oncogene volume 21, pages 6395–6402 (2002)Cite this article

Abstract

The locus for a syndrome of focal palmoplantar keratoderma (Tylosis) associated with squamous cell oesophageal cancer (TOC) has been mapped to chromosome 17q25, a region frequently deleted in sporadic squamous cell oesophageal tumours. Further haplotype analysis described here, based on revised maps of marker order, has reduced the TOC minimal region to a genetic interval of 2 cM limited by the microsatellite markers D17S785 and D17S751. Partial sequence data and complete physical maps estimate the actual size of this region to be only 0.5 Mb. This analysis allowed the exclusion of proposed candidate tumour suppressor genes including MLL septin-like fusion (MSF), survivin, and deleted in multiple human cancer (DMC1). Computer analysis of sequence data from the minimal region identified 13 candidate genes and the presence of 50–70 other ‘gene fragments’ as ESTs and/or predicted exons and genes. Ten of the characterized genes were assayed for mutations but no disease-specific alterations were identified in the coding and promoter sequences. This region of chromosome 17q25 is, therefore, relatively gene-rich, containing 13 known and possibly as many as 50 predicted genes. Further mutation analysis of these predicted genes, and others possibly residing in the region, is required in order to identify the elusive TOC locus.

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Acknowledgements

The authors wish to thank Dr G Kuhlenbäumer, Professor C Van Broeckhoven and Professor E Petty for their release to us of pre-publication data. This work was supported by grants from the Cancer Research Campaign (CRC) (grant numbers SP2384/0101 and SP2384/0201), the North West Cancer Research Fund, Isle of Man Anti Cancer Association, and a University of Liverpool PhD studentship.

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Authors and Affiliations

  1. Department of Clinical Dental Sciences, Molecular Genetics and Oncology Group, The University of Liverpool, Liverpool, L69 3GN, UK

    Janet M Risk, Kathryn E Evans, Joanne Jones, Joanne E Langan, Lyn Rowbottom, Fiona E McRonald, Helen S Mills & John K Field

  2. Department of Gastroenterology, Royal Liverpool University Hospital, Prescot Street, Liverpool, L7 8XP, UK

    Anthony Ellis & Joan M Shaw

  3. Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, University of London, 2 Newark Street, London, E1 2AT, UK

    Irene M Leigh & David P Kelsell

  4. Roy Castle International Centre for Lung Cancer Research, London Road, Liverpool, L3 9TA, UK

    John K Field

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  1. Janet M Risk
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Correspondence to Janet M Risk.

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Risk, J., Evans, K., Jones, J. et al. Characterization of a 500 kb region on 17q25 and the exclusion of candidate genes as the familial Tylosis Oesophageal Cancer (TOC) locus. Oncogene 21, 6395–6402 (2002). https://doi.org/10.1038/sj.onc.1205768

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