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Somatic loss of polycystic disease genes contributes to the formation of isolated and polycystic liver cysts
  1. Manoe J Janssen1,
  2. Jody Salomon1,
  3. Wybrich R Cnossen1,
  4. Carsten Bergmann2,3,
  5. Rolph Pfundt4,
  6. Joost P H Drenth1
  1. 1Department of Gastroenterology & Hepatology, Radboudumc, Institute for Genetic and Metabolic Diseases, Nijmegen, The Netherlands
  2. 2Department of Bioscientia, Center for Human Genetics, Ingelheim, Germany
  3. 3Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany
  4. 4Department of Human Genetics, Radboudumc, Institute for Genetic and Metabolic Diseases, Nijmegen, The Netherlands
  1. Correspondence to Professor Joost P H Drenth, Department of Gastroenterology & Hepatology, Radboudumc, Institute for Genetic and Metabolic Diseases, P.O. Box 9101, code 455, Nijmegen 6500hb, The Netherlands; joostphdrenth{at}cs.com

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We read with interest the paper by Urribarri et al1 which describes that metalloprotease hyperactivity plays an important role in cyst expansion and that metalloprotease inhibition reduces cyst proliferation. As such, these results help to identify potential drug targets.2 We hypothesise that the expansion and maintenance of the cyst is preceded by mutational events that trigger cytogenesis, and we used genetic analysis to provide additional insight into this process. The majority of polycystic diseases are autosomal dominant disorders where every patient cell possesses one germ line mutation (first hit).3 As somatic second-hit mutations play an important role in liver and renal cyst formation,4–6 it was hypothesised that patients with polycystic disease have a DNA repair defect and accumulate somatic mutations.7 This was supported by a comparative genomic hybridisation study where renal cysts harboured multiple chromosomal aberrations, similar to cancers.8 ,9 In addition, patients without a germ line mutation can still develop …

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