Detection of promoter hypermethylation of tumor suppressor genes in urine from kidney cancer patients.
Kidney cancer is curable by surgical resection and therapy, if detected at an early stage. Using sensitive methylation-specific polymerase chain reaction, we screened matched tumor DNA and preoperative urine DNA from 50 kidney cancer patients, for hypermethylation of a panel of six normally unmethylated tumor suppressor genes: VHL, p16/CDKN2a, p14ARF, APC, RASSF1A, and Timp-3. When compared to the tumor DNA, an identical pattern of gene hypermethylation was found in the matched urine DNA from 44 of 50 patients (88% sensitivity) including 27 of 30 cases of stage I disease. By contrast, hypermethylation was not observed in normal and benign disease controls (100% specificity). We conclude that promoter hypermethylation is a common and early event in kidney tumorigenesis and can be detected in the urine DNA from patients with organ-confined renal cancer of all histologic types.
Cairns
Paul
P
Fox Chase Cancer Center, Surgical Oncology & Pathology, Philadelphia, Pennsylvania 19111, USA. P_Cairns@fccc.edu
D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000652:urine*; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm