RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking.
RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking.
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DOI：
10.1158/0008-5472.can-07-6616
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发表时间：
2008-08-01
期刊：
影响因子：
11.2
通讯作者：
Jones PA
中科院分区：
文献类型：
--
作者：
Wolff EM;Liang G;Cortez CC;Tsai YC;Castelao JE;Cortessis VK;Tsao-Wei DD;Groshen S;Jones PA
Exposure to tobacco smoke is associated with increased DNA methylation at certain genes in both lung and bladder tumors. We sought to identify interactions in bladder cancer between DNA methylation and a history of smoking, along with any possible effect of aging. We measured DNA methylation in 342 transitional cell carcinoma (TCC) tumors at BCL2, PTGS2 (COX2), DAPK, CDH1 (ECAD), EDNRB, RASSF1A, RUNX3, TERT, and TIMP3. The prevalence of methylation at RUNX3, a polycomb target gene, increased as a function of age at diagnosis (p=0.031) and a history of smoking (p=0.015). RUNX3 methylation also preceded methylation at the other 8 genes (p<0.001). It has been proposed that DNA methylation patterns constitute a “molecular clock” and can be used to determine the “age” of normal tissues, i.e., the number of times the cells have divided. Since RUNX3 methylation increases with age, is not present in normal urothelium, and occurs early in tumorigenesis, it can be used for the first time as a molecular clock in order to determine the age of a bladder tumor. Doing so reveals that tumors from smokers are “older” than tumors from nonsmokers (p=0.009) either due to tumors in smokers initiating earlier or undergoing more rapid cell divisions. Since RUNX3 methylation is acquired early on in tumorigenesis then its detection in biopsy or urine specimens could provide a marker to screen cigarette smokers long before any symptoms of bladder cancer are present.
