SOMATIC MUTATION IN INDIVIDUAL LIVER CYSTS SUPPORTS A 2-HIT MODEL OF CYSTOGENESIS IN AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE

Autosomal dominant polycystic kidney disease (ADPKD), Type I is a comm on genetic disorder and an important cause of renal failure. The disea se is characterized by progressive cyst formation in a variety of orga ns including the kidney, liver and pancreas. We have previously shown that in the case of PKD1, renal cyst development is likely to require somatic inactivation of the normal allele coupled to a germline PKD1 m utation. In this report, we have used unique reagents to show that int ragenic, somatic mutations are common in hepatic cysts. All pathogenic mutations were shown to have altered the previously normal copy of th e gene. These data extend the ''two-hit'' model of cystogenesis to inc lude a second focal manifestation of the disease.