PTEN loss is associated with prostate cancer recurrence and alterations in tumor DNA methylation profiles.
PTEN loss is associated with prostate cancer recurrence and alterations in tumor DNA methylation profiles.
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DOI：
10.18632/oncotarget.20940
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发表时间：
2017-10-13
期刊：
影响因子：
--
通讯作者：
Stanford JL
中科院分区：
文献类型：
--
作者：
Geybels MS;Fang M;Wright JL;Qu X;Bibikova M;Klotzle B;Fan JB;Feng Z;Ostrander EA;Nelson PS;Stanford JL
肿瘤抑制基因PTEN缺失的前列腺癌预后不良。与PTEN缺失相关的DNA甲基化谱可能为这些更具侵袭性的临床相关肿瘤的机制提供进一步的见解。该队列包括临床局限性PCa患者。从原发性肿瘤中采集的样品用于使用FISH确定PTEN基因组缺失，并分析表观基因组范围的DNA甲基化谱。患者在诊断后平均随访8年，以了解PCa复发情况。该研究包括471例有PTEN丢失数据的患者，半合子和纯合子PTEN丢失的频率分别为10.0%和4.5%。PTEN缺失与显著更高的复发风险相关（任何与无PTEN缺失; HR = 1.74; 95%CI：1.03-2.93）。半合子和纯合子丢失的风险比分别为1.39（95% CI：0.73-2.64）和2.84（95% CI：1.30-6.19）。表观基因组范围的甲基化分析在具有任何与没有PTEN损失的肿瘤中鉴定了4，208个差异甲基化的CpG（FDR Q值< 0.01）。在同源与半合子缺失肿瘤中没有全基因组显著差异甲基化的CpG。肿瘤甲基化数据用于建立我们的队列中PTEN丢失的甲基化特征，其在TCGA中得到证实，并且包括ATP 11 A、GDNF、JAK 1、JAM 3和VAPA中的CpG。PTEN缺失与PCa复发呈正相关。具有PTEN缺失的前列腺肿瘤具有独特的甲基化特征，并且当PTEN缺失时，这些异常甲基化的CpG位点可能介导肿瘤进展。
Prostate cancer (PCa) with loss of the tumor suppressor gene PTEN has an unfavorable prognosis. DNA methylation profiles associated with PTEN loss may provide further insights into the mechanisms underlying these more aggressive, clinically relevant tumors. The cohort included patients with clinically localized PCa. Samples taken from the primary tumor were used to determine PTEN genomic deletions using FISH, and to analyze epigenome-wide DNA methylation profiles. Patients were followed for PCa recurrence on average for 8 years after diagnosis. The study included 471 patients with data on PTEN loss, and the frequency of hemi- and homozygous PTEN loss was 10.0% and 4.5%, respectively. Loss of PTEN was associated with a significantly higher risk of recurrence (any vs. no PTEN loss; HR = 1.74; 95% CI: 1.03–2.93). Hazard ratios for hemi- and homozygous loss were 1.39 (95% CI: 0.73–2.64) and 2.84 (95% CI: 1.30–6.19), respectively. Epigenome-wide methylation profiling identified 4,208 differentially methylated CpGs (FDR Q-value < 0.01) in tumors with any versus no PTEN loss. There were no genome-wide significant differentially methylated CpGs in homo- versus hemizygous deleted tumors. Tumor methylation data were used to build a methylation signature of PTEN loss in our cohort, which was confirmed in TCGA, and included CpGs in ATP11A, GDNF, JAK1, JAM3, and VAPA. Loss of PTEN was positively associated with PCa recurrence. Prostate tumors with PTEN loss harbor a distinct methylation signature, and these aberrantly methylated CpG sites may mediate tumor progression when PTEN is deleted.
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影响因子：
30.8
作者：
Carver, Brett S.;Tran, Jennifer;Gopalan, Anuradha;Chen, Zhenbang;Shaikh, Safa;Carracedo, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Varmeh, Shohreh;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
--
作者：
Huber RM;Lucas JM;Gomez-Sarosi LA;Coleman I;Zhao S;Coleman R;Nelson PS
通讯作者：
Nelson PS
影响因子：
17.1
作者：
Aryee MJ;Liu W;Engelmann JC;Nuhn P;Gurel M;Haffner MC;Esopi D;Irizarry RA;Getzenberg RH;Nelson WG;Luo J;Xu J;Isaacs WB;Bova GS;Yegnasubramanian S
通讯作者：
Yegnasubramanian S
影响因子：
5.7
作者：
Geybels MS;Wright JL;Bibikova M;Klotzle B;Fan JB;Zhao S;Feng Z;Ostrander EA;Lin DW;Nelson PS;Stanford JL
通讯作者：
Stanford JL