Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma

摘要: Abstract Mutational inactivation and allelic loss of the von Hippel-Lindau (VHL) gene appear to be causal events for majority spontaneous clear-cell renal carcinomas. We now show that hypermethylation a normally unmethylated CpG island in 5' region provides another potentially important mechanism VHL significant portion these cancers. This was found 5 26 (19%) tumors examined. Four had lost one copy while retained two heavily methylated alleles. with no detectable mutations, whereas missense mutation addition single allele. As would predicted consequence methylation this island, none expressed gene. In contrast, normal kidney all examined inactivating mutations but expression. cell culture line, treatment 5-aza-2'-deoxycytidine resulted reexpression These findings suggest aberrant islands may participate tumor-suppressor inactivations which initiate or cause progression common human