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Metaplasia and neoplasia
Analysis of genetic and phenotypic heterogeneity in juvenile polyposis
  1. K Woodford-Richensa,
  2. S Bevanb,
  3. M Churchmanc,
  4. B Dowlingc,
  5. D Jonesd,
  6. C G Norburyd,
  7. S V Hodgsone,
  8. D Desaif,
  9. K Nealef,
  10. R K S Phillipsf,
  11. J Youngg,
  12. B Leggettg,
  13. M Dunloph,
  14. P Rozeni,
  15. C Engj,
  16. D Markiek,
  17. M A Rodriguez-Bigasl,
  18. E Sheridanm,
  19. T Iwaman,
  20. D Eccleso,
  21. G T Smithp,
  22. J C Kimq,
  23. K M Kimq,
  24. J R Sampsonr,
  25. G Evanss,
  26. S Tejpart,
  27. W F Bodmeru,
  28. I P M Tomlinsona,
  29. R S Houlstonb
  1. aMolecular and Population Genetics Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK, bCancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK, cTumour Genetics Group, Nuffield Department of Clinical Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Windmill Road, Oxford OX3 7BN, UK, dMolecular Genetics Laboratory, Churchill Hospital, Oxford OX3 7LJ, UK, eDepartment of Clinical Genetics, Guy's Hospital, St Thomas's Street, London SE1 9RT, UK, fPolyposis Registry, St Mark's Hospital, Watford Road, Harrow HA1 3UJ, UK, gQueensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, Australia, hMRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK, iDepartment of Gastroenterology, Tel Aviv Medical Center and Medical School, IL-64239 Tel Aviv, Israel, jHuman Cancer Genetics Program, Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA, kMolecular Genetics Laboratory, Pathology Department, Dunedin School of Medicine, Dunedin, New Zealand, lRoswell Park Cancer Institute, Buffalo, New York 14263, USA, mDepartment of Clinical Genetics, Royal Hospital for Children, St Michael's Hill, Bristol, UK, nCentre for Polyposis and Intestinal Diseases, 1–5–45, Yushima, Bunkyo-Ku, Tokyo 113, Japan, oWessex Regional Genetics Service, Southampton SO16 5YA, UK, pDepartment of Histopathology, Worcester Royal Infirmary, WR1 3AS, UK, qDepartment of Paediatrics, University of Ulsan College of Medicine, and Asan Institute, Seoul, Korea, rInstitute of Medical Genetics, University of Wales College of Medicine, Cardiff CF4 4XN, UK, sRegional Genetic Service, St Mary's Hospital, Manchester M13 0JH, UK, tCentre for Human Genetics, Campus Gasthuisberg, O and N6, B-3000, Leuven, Belgium, uCancer Immuno-genetics Laboratory, ICRF, Institute of Molecular Medicine, Oxford OX3 9DS, UK
  1. R Houlston, Haddow Laboratories, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. Email:r.houlston{at}icr.ac.uk

Abstract

BACKGROUND Juvenile polyposis syndrome (JPS) is characterised by gastrointestinal (GI) hamartomatous polyposis and an increased risk of GI malignancy. Juvenile polyps also occur in the Cowden (CS), Bannayan-Ruvalcaba-Riley (BRRS) and Gorlin (GS) syndromes. Diagnosing JPS can be problematic because it relies on exclusion of CS, BRRS, and GS. Germline mutations in the PTCH, PTENand DPC4 (SMAD4)genes can cause GS, CS/BRRS, and JPS, respectively.

AIMS To examine the contribution of mutations in PTCH,PTEN, and DPC4(SMAD4) to JPS.

METHODS Forty seven individuals from 15 families and nine apparently sporadic cases with JPS were screened for germline mutations inDPC4, PTEN, andPTCH.

RESULTS No patient had a mutation in PTEN orPTCH. Five different germline mutations were detected in DPC4; three of these were deletions, one a single base substitution creating a stop codon, and one a missense change. None of these patients had distinguishing clinical features.

CONCLUSIONS Mutations in PTEN and PTCHare unlikely to cause juvenile polyposis in the absence of clinical features indicative of CS, BRRS, or GS. A proportion of JPS patients harbour DPC4 mutations (21% in this study) but there remains uncharacterised genetic heterogeneity in JPS.

  • juvenile polyposis syndrome
  • germline mutations

https://doi.org/10.1136/gut.46.5.656

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    Footnotes

    • Abbreviations used in this paper:
      JPS
      juvenile polyposis syndrome
      CS
      Cowden syndrome
      BRRS
      Bannayan-Ruvalcaba-Riley syndrome
      GS
      Gorlin syndrome
      CSGE
      conformation specific gel electrophoresis
      SSCP
      single strand conformational gel polymorphism