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Indication for CDKN2A-mutation analysis in familial pancreatic cancer families without melanomas
  1. Femme Harinck1,
  2. Irma Kluijt2,
  3. Nienke van der Stoep3,
  4. Rogier A Oldenburg4,
  5. Anja Wagner4,
  6. Cora M Aalfs5,
  7. Rolf H Sijmons6,
  8. Jan-Werner Poley1,
  9. Ernst J Kuipers1,7,
  10. Paul Fockens8,
  11. Theo A M van Os5,
  12. Marco J Bruno1
  1. 1Department of Gastroenterology & Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands
  2. 2Family Cancer Clinic, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  3. 3Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
  4. 4Department of Clinical Genetics, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands
  5. 5Department of Clinical Genetics, Academic Medical Center-University of Amsterdam, Amsterdam, The Netherlands
  6. 6Department of Clinical Genetics, University Medical Center Groningen-University of Groningen, Groningen, The Netherlands
  7. 7Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands
  8. 8Department of Gastroenterology & Hepatology, Academic Medical Center-University of Amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Dr Femme Harinck, Erasmus MC-University Medical Center Rotterdam, Department of Gastroenterology & Hepatology, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands; f.harinck{at}


Background CDKN2A-mutation carriers run a high risk of developing melanomas and have an increased risk of developing pancreatic cancer (PC). Familial PC (FPC) patients with a personal history or family history of melanomas are therefore offered CDKN2A-mutation analysis. In contrast, CDKN2A testing in FPC families without a history of melanomas is not generally recommended. The aim of this study was to evaluate the frequency of CDKN2A-mutations in FPC families without melanomas.

Methods Data were gathered from PC family registers. FPC families were defined as families with clustering of PC without meeting diagnostic criteria of familial cutaneous malignant melanoma (familial CMM) or other inherited cancer syndromes. Blood samples were obtained for DNA isolation from PC patients or first degree relatives and analysed for CDKN2A-mutations.

Results Among 40 FPC families, DNA analyses were carried out in 28 families (70%), leading to identification of CDKN2A-mutations in six families (21%). None of the CDKN2A-mutation-positive families fulfilled the diagnostic criteria for familial CMM and in three CDKN2A families no melanomas were observed. Two CDKN2A-mutations were found; the Dutch founder mutation p16-Leiden (c.225_243del, p.Ala76fs) and the c.19_23dup, p.Ser8fs-mutation. After disclosure of the CDKN2A-mutation in one of the families, a curable melanoma was diagnosed at dermatological surveillance in a 17-year-old family member.

Conclusion CDKN2A-mutation can be found in a considerable proportion of families with FPC. CDKN2A-mutation analysis should therefore be included in genetic testing in FPC families, even in the absence of reported melanomas. This strategy will enhance the recognition of individuals at risk for PC and facilitate the early detection of melanomas.

  • Pancreatic cancer
  • inherited cancer
  • mutations
  • cancer susceptibility
  • cancer prevention
  • cancer: dermatological
  • diagnosis
  • diagnostics tests
  • genetic screening/counselling
  • prevention

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  • Competing interests None.

  • Ethics approval Approval provided by the Ethics Committee Erasmus MC, Ethics Committee AMC, Ethics Committee NKI/AvL, Ethics Committee UMCG.

  • Provenance and peer review Not commissioned; externally peer reviewed.