Coordinate hypermethylation at specific genes in prostate carcinoma precedes LINE-1 hypomethylation.
Coordinate hypermethylation at specific genes in prostate carcinoma precedes LINE-1 hypomethylation.
复制标题
DOI：
10.1038/sj.bjc.6602030
复制
发表时间：
2004-08-31
影响因子：
8.8
通讯作者：
Schulz, WA
中科院分区：
文献类型：
--
作者：
Florl, AL;Steinhoff, C;Müller, M;Seifert, HH;Hader, C;Engers, R;Ackermann, R;Schulz, WA
在前列腺癌（PCa）中，DNA甲基化（“超甲基化”）发生在特定基因，如GSTP 1。然而，由于重复序列如LINE-1逆转录转座子的甲基化减少，整体甲基化可以降低（“低甲基化”）。我们分析了DNA从113 PCa和36非癌前列腺组织LINE-1低甲基化的敏感的Southern技术和甲基化特异性PCR在8个位点的超甲基化。癌组织中GSTP 1、RARB 2、RASSF 1A和APC的高甲基化频率均> 70%，彼此之间存在强相关性（P<10−6）。每个基因座的超甲基化在肿瘤和正常组织之间存在显著差异（10−11<P<103），尽管在非癌组织中也观察到了超甲基化，特别是RASSF 1A。ASC 1高甲基化在同时发生高甲基化的PCa亚组中观察到。CDH 1、CDKN 2A和SFRP 1的高甲基化是罕见的。LINE-1低甲基化在49%的PCa中检测到，所有在几个位点都有高甲基化。它与肿瘤分期显著相关，而高甲基化与肿瘤分期和Gleason评分均不相关。几个基因的协调高甲基化可能发生在PCa的早期，额外的高甲基化事件和LINE-1低甲基化与进展相关。超甲基化允许检测>82%的PCas。PCa可以分为三类，即具有很少的DNA甲基化变化，具有频繁的超甲基化，或具有额外的LINE-1低甲基化。
In prostate carcinoma (PCa) increased DNA methylation (‘hypermethylation’) occurs at specific genes such as GSTP1. Nevertheless, overall methylation can be decreased (‘hypomethylation’) because methylation of repetitive sequences like LINE-1 retrotransposons is diminished. We analysed DNA from 113 PCa and 36 noncancerous prostate tissues for LINE-1 hypomethylation by a sensitive Southern technique and for hypermethylation at eight loci by methylation-specific PCR. Hypermethylation frequencies for GSTP1, RARB2, RASSF1A, and APC in carcinoma tissues were each >70%, strongly correlating with each other (P<10−6). Hypermethylation at each locus was significantly different between tumour and normal tissues (10−11<P<103), although hypermethylation, particularly of RASSF1A, was also observed in noncarcinoma tissues. ASC1 hypermethylation was observed in a subgroup of PCa with concurrent hypermethylation. Hypermethylation of CDH1, CDKN2A, and SFRP1 was rare. LINE-1 hypomethylation was detected in 49% PCa, all with hypermethylation at several loci. It correlated significantly with tumour stage, while hypermethylation was neither related to tumour stage nor Gleason score. Coordinate hypermethylation of several genes may occur early in PCa, with additional hypermethylation events and LINE-1 hypomethylation associated with progression. Hypermethylation allows detection of >82% of PCas. PCa may fall into three classes, that is, with few DNA methylation changes, with frequent hypermethylation, or with additional LINE-1 hypomethylation.
登录
查看更多内容
DOI：
10.1073/pnas.97.2.710
发表时间：
2000-01-18
影响因子：
11.1
作者：
Toyota, M;Ohe-Toyota, M;Issa, JPJ
通讯作者：
Issa, JPJ
影响因子：
8
作者：
Millar, DS;Ow, KK;Clark, SJ
通讯作者：
Clark, SJ
影响因子：
30.8
作者：
Suzuki, H;Gabrielson, E;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
3.7
作者：
Schulz, WA;Elo, JP;Visakorpi, T
通讯作者：
Visakorpi, T
影响因子：
2.8
作者：
Woodson, K;Hayes, R;Tangrea, J
通讯作者：
Tangrea, J