Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array
Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array
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DOI：
10.1002/gcc.20369
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发表时间：
2006-11-01
影响因子：
3.7
通讯作者：
Xu, Jianfeng
中科院分区：
文献类型：
--
作者：
Liu, Wennuan;Chang, Baoli;Xu, Jianfeng
虽然在前列腺癌细胞中已经发现了多个复发性染色体改变，但驱动这些改变的明显选择的特定基因在很大程度上仍然未知。在某种程度上，这种不确定性是由于用于检测这些改变的技术的分辨率有限。在这项研究中，我们应用了一种高分辨率的全基因组方法，Affytelium 100 K SNIP作图阵列，在22对原发性前列腺癌和匹配的非恶性组织样本中筛选体细胞DNA拷贝数（CN）的改变。我们检测到355个复发性缺失和223个复发性增益，其中许多是新的。正如预期的那样，新的改动的尺寸往往较小。重要的是，在Gleason总和为6、7和8级的肿瘤中，我们发现在较高级别的肿瘤中有较大数量的变化的显著趋势。总的来说，增益更有可能发生在基因（74%）比删除（49%）。然而，当我们观察最常见的CN改变时，定义为>= 4个受试者，我们观察到增益（85%）和缺失（57%）都优先发生在基因内。本研究中观察到的一个新的复发性改变的例子是21号染色体上ERG和TMPRSS 2基因之间的缺失，推测与最近鉴定的这两个基因的融合转录物有关。本研究的结果为系统和全面地编目与前列腺癌分级相关的CN改变以及随后鉴定与疾病发生和进展相关的特定基因提供了基础。本文包含可通过互联网http://www.interscience.wiley获得的补充材料。com/jpages/1045-2257/suppmat（c）2006 Wiley-Liss，Inc.
Although multiple recurrent chromosomal alterations have been identified in prostate cancer cells, the specific genes driving the apparent selection of these changes remain largely unknown. In part, this uncertainty is due to the limited resolution of the techniques used to detect these alterations. In this study, we applied a high-resolution genome-wide method, Affymetrix 100K SNIP mapping array, to screen for somatic DNA copy number (CN) alterations among 22 pairs of samples from primary prostate cancers and matched nonmalignant tissues. We detected 355 recurrent deletions and 223 recurrent gains, many of which were novel. As expected, the sizes of novel alterations tend to be smaller. Importantly, among tumors with increasing grade, Gleason sum 6, 7, and 8, we found a significant trend of larger number of alterations in the tumors with higher grade. Overall, gains are significantly more likely to occur within genes (74%) than are deletions (49%). However, when we looked at the most frequent CN alterations, defined as those in >= 4 subjects, we observed that both gains (85%) and deletions (57%) occur preferentially within genes. An example of a novel, recurrent alteration observed in this study was a deletion between the ERG and TMPRSS2 genes on chromosome 21, presumably related to the recently identified fusion transcripts from these two genes. Results from this study provide a basis for a systematic and comprehensive cataloging of CN alterations associated with grades of prostate cancer, and the subsequent identification of specific genes that associated with initiation and progression of the disease. This article contains supplementary material available via the Internet at http://www.interscience.wiley. com/jpages/1045-2257/suppmat (c) 2006 Wiley-Liss, Inc.