作者: Sarah A Bowden , Euan J Rodger , Michael Bates , Aniruddha Chatterjee , Michael R Eccles
DOI: 10.1159/000494739
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摘要: Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the formation of fluid-filled cysts in and end stage renal fourth or fifth decade life. Mutations PKD1 gene account for 85% all cases ADPKD. No curative therapy exists patients affected this an underexplored avenue treatment ADPKD targeting epigenetic changes that occur during cystogenesis. Limited data on alterations DNA methylation are associated with Given similarities between cyst growth neoplasia, fact 2 inhibitors already Food Drug Administration-approved myelodysplastic syndrome, we hypothesized global patterns would parallel observed which may provide opportunity to treat inhibitors. To address hypothesis, undertook a analysis human kidney. Methods We generated single nucleotide resolution methylomes cortical tissue from individuals ADPKD, non-ADPKD tissue, using reduced representation bisulfite sequencing. Using quantitative reverse transcription polymerase chain reaction, investigated expression both Results have shown ADPKD-derived genomic exhibits hypomethylation when compared kidney, pattern commonly studies tumor-derived tissue. also identified 13 discrete regions significantly differentially methylated non-ADPKD, 8 these specific. The shows increase at 3' body, but contrast previously published data, not decrease mRNA expression. Conclusion This genome-scale kidneys suggests differences specific loci Further exploration into significance preliminary results shed light process, potentially reveal new therapeutic possibilities.