Comprehensive analysis of 20q13 genes in ovarian cancer identifies ADRM1 as amplification target
Comprehensive analysis of 20q13 genes in ovarian cancer identifies ADRM1 as amplification target
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DOI：
10.1002/gcc.20592
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发表时间：
2008-10-01
影响因子：
3.7
通讯作者：
Slamon, Dennis J.
中科院分区：
文献类型：
--
作者：
Fejzo, Marlena S.;Dering, Judy;Slamon, Dennis J.
在美国，每年大约有25，000例卵巢癌被诊断出来，其中75%的病例处于晚期，基本上无法治愈。迫切需要改进的早期检测工具和开发新的治疗方法。由于染色体带20 q13是卵巢癌中常见的DNA扩增区域，并且20 q13拷贝数的增加可能是早期事件，我们检查了定位到该区域的239个微阵列探针的DNA扩增和RNA表达模式，目的是鉴定与卵巢癌相关的基因。我们将候选基因缩小到19个，这些基因在ZNF 217和TPD 54扩增的肿瘤亚组中持续过表达，尽管有趣的是，候选基因不包括这两个扩增的基因。对225个卵巢样本的这19个基因的RNA表达进行无监督聚类，可以鉴定出51个（23%）肿瘤的20 q扩增子集，该子集与不良结局显著相关。在该亚组的19个候选基因中，ADRM 1过表达与扩增的相关性最高，在肿瘤中的扩增百分比高于ZNF 217和TPD 54，并且在分期、复发和转移方面显著上调。此外，ADRM 1的过表达与较短的复发时间和总生存率显著相关，现在需要进行功能分析以确定ADRM 1是否是卵巢癌早期筛查和/或治疗的靶点。(C)2008 Wiley-Liss，Inc.
Approximately 25,000 ovarian cancers are diagnosed in the US annually, and 75% of cases are in the advanced stage when they are largely incurable. There is a critical need for improved early detection tools and development of novel treatments. Because chromosome band 20q13 is a commonly DNA amplified region in ovarian cancer and increase in 20q13 copy number may be an early event, we examined the DNA amplification and RNA expression pattern of 239 microarray probes mapping to this region with the goal of identifying gene(s) associated with ovarian cancer Using Agilent expression microarray analysis and FISH to tumor tissue arrays, we narrowed the candidates to 19 genes that were consistently overexpressed in a subset of tumors amplified for both ZNF217 and TPD54, although, interestingly the candidates do not include these two amplified genes. Unsupervised clustering of 225 ovarian samples with respect to RNA expression of these 19 genes allowed identification of a 20q-amplified subset of 51 (23%) tumors and this subset was significantly correlated with poor outcome. Of the 19 candidate genes in this subset, ADRM1 overexpression was the most highly correlated with amplification, was amplified in a higher percentage of tumors than ZNF217 and TPD54, and was significantly upregulated with respect to stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlates significantly with shorter time to recurrence and overall survival, Functional analysis is now warranted to determine whether ADRM1 is a target for early screening and/or therapy for ovarian cancer. (C) 2008 Wiley-Liss, Inc.