膀胱癌
神经母细胞瘤RAS病毒癌基因同源物
DNA甲基化
克拉斯
赫拉
甲基化
表观遗传学
癌症研究
生物
癌症
突变
病理
医学
基因
遗传学
基因表达
作者
Reza Serizawa,Ulrik Ralfkiær,Kenneth Steven,Gitte Wrist Lam,Sven Schmiedel,Joachim Schüz,Alastair Hansen,Thomas Horn,Per Guldberg
摘要
Abstract The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically screened FGFR3 , PIK3CA , TP53 , HRAS , NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC , ARF , DBC1 , INK4A , RARB , RASSF1A , SFRP1 , SFRP2 , SFRP4 , SFRP5 and WIF1 in a prospective series of tumor biopsies ( N = 105) and urine samples ( N = 113) from 118 bladder tumor patients. We also analyzed urine samples from 33 patients with noncancerous urinary lesions. A total of 95 oncogenic mutations and 189 hypermethylation events were detected in the 105 tumor biopsies. The total panel of markers provided a sensitivity of 93%, whereas mutation and methylation markers alone provided sensitivities of 72% and 70%, respectively. In urine samples, the sensitivity was 70% for all markers, 50% for mutation markers and 52% for methylation markers. FGFR3 mutations occurred more frequently in tumors with no methylation events than in tumors with one or more methylation events (78% vs . 33%; p < 0.0001). FGFR3 mutation in combination with three methylation markers ( APC , RASSF1A and SFRP2 ) provided a sensitivity of 90% in tumors and 62% in urine with 100% specificity. These results suggest an inverse correlation between FGFR3 mutations and hypermethylation events, which may be used to improve noninvasive, DNA‐based detection of bladder cancer.
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