Somatic PKD2 mutations in individual kidney and liver cysts support a 'two-hit' model of cystogenesis in type 2 autosomal dominant polycystic kidney disease

York Pei, Terry Watnick, Ning He, Kairong Wang, Yan Liang, Patrick Parfrey, Gregory Germino, Peter St. George-Hyslop

Research output: Contribution to journalArticle

Abstract

An intriguing feature of autosomal dominant polycystic kidney disease (ADPKD) is the focal and sporadic formation of renal and extrarenal cysts. Recent documentation of somatic PKD1 mutations in cystic epithelia of patients with germ-line PKD1 mutations suggests a 'two-hit' model for cystogenesis in type 1 ADPKD. This study tests whether the same mechanism for cystogenesis might also occur in type 2 ADPKD. Genomic DNA was obtained from 54 kidney and liver cysts from three patients with known germ-line PKD2 mutations, using procedures that minimize contamination of cells from noncystic tissue. Using intragenic and microsatellite markers, these cyst samples were screened for loss of heterozygosity. The same samples were also screened for somatic mutations in five of the 15 exons in PKD2 by single- stranded conformational polymorphism analysis. Loss of heterozygosity was found in five cysts, and unique intragenic mutations were found in seven other cysts. In 11 of these 12 cysts, it was also determined that the somatic mutation occurred nonrandomly in the copy of PKD2 inherited from the unaffected parent. These findings support the 'two-hit' model as a unified mechanism for cystogenesis in ADPKD. In this model, the requirement of a somatic mutation as the rate-limiting step for individual cyst formation has potential therapeutic implications.

Original languageEnglish (US)
Pages (from-to)1524-1529
Number of pages6
JournalJournal of the American Society of Nephrology
Volume10
Issue number7
StatePublished - Jul 1999

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Autosomal Dominant Polycystic Kidney
Cysts
Kidney
Mutation
Liver
Germ-Line Mutation
Loss of Heterozygosity
Single-Stranded Conformational Polymorphism
Mutation Rate
Documentation
Microsatellite Repeats
Exons
Epithelium
DNA

ASJC Scopus subject areas

  • Nephrology

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Somatic PKD2 mutations in individual kidney and liver cysts support a 'two-hit' model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. / Pei, York; Watnick, Terry; He, Ning; Wang, Kairong; Liang, Yan; Parfrey, Patrick; Germino, Gregory; St. George-Hyslop, Peter.

In: Journal of the American Society of Nephrology, Vol. 10, No. 7, 07.1999, p. 1524-1529.

Research output: Contribution to journalArticle

Pei, Y, Watnick, T, He, N, Wang, K, Liang, Y, Parfrey, P, Germino, G & St. George-Hyslop, P 1999, 'Somatic PKD2 mutations in individual kidney and liver cysts support a 'two-hit' model of cystogenesis in type 2 autosomal dominant polycystic kidney disease', Journal of the American Society of Nephrology, vol. 10, no. 7, pp. 1524-1529.
Pei, York ; Watnick, Terry ; He, Ning ; Wang, Kairong ; Liang, Yan ; Parfrey, Patrick ; Germino, Gregory ; St. George-Hyslop, Peter. / Somatic PKD2 mutations in individual kidney and liver cysts support a 'two-hit' model of cystogenesis in type 2 autosomal dominant polycystic kidney disease. In: Journal of the American Society of Nephrology. 1999 ; Vol. 10, No. 7. pp. 1524-1529.
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