Ploidy status and copy number aberrations in primary glioblastomas defined by integrated analysis of allelic ratios, signal ratios and loss of heterozygosity using 500K SNP Mapping Arrays.
Ploidy status and copy number aberrations in primary glioblastomas defined by integrated analysis of allelic ratios, signal ratios and loss of heterozygosity using 500K SNP Mapping Arrays.
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使用500K SNP映射阵列对等位基因比，信号比和杂合性损失的综合分析定义的主要胶质母细胞瘤中的倍性状态和拷贝数畸变。
DOI：
10.1186/1471-2164-9-489
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发表时间：
2008-10-17
期刊：
影响因子：
4.4
通讯作者：
Turpaz, Yaron
中科院分区：
文献类型：
--
作者：
Gardina, Paul J.;Lo, Ken C.;Lee, Walter;Cowell, John K.;Turpaz, Yaron
基因组杂交平台，包括 BAC-CGH 和基因分型阵列，已被用于通过检测基因组信号的相对强度来估计肿瘤样本中的染色体拷贝数 (CN)。这些方法依赖于样品的主要染色体背景是二倍体的假设，这种假设对于肿瘤样品来说通常是不正确的。除了普遍更高的分辨率之外，基因分型芯片相对于 CGH 芯片的一个优点是能够检测来自单个等位基因的信号，从而可以估计杂合性丢失 (LOH) 和等位基因比率，以增强对拷贝数改变的解释。与 LOH 相关的拷贝数事件可能与缺失具有相同的遗传后果。我们利用等位基因比率来检测指示较高倍性水平的模式。使用等位基因比率、总信号和 LOH 的综合分析表明，24 个胶质母细胞瘤肿瘤的许多或大部分染色体实际上是非整倍体。一些假定的全染色体丢失实际上代表三体性，许多明显的亚染色体丢失实际上是相对于三倍体或四倍体背景的相对丢失。这些结果表明仅根据总信号比重新解释先前的发现。一个有趣的观察是，在染色体复制之后，许多单拷贝或多拷贝缺失发生在常见的假定肿瘤抑制位点；这些损失并不一定会导致 LOH，但仍然以明显的模式发生。 500 K Mapping 阵列还能够检测 CGH-BAC 阵列忽略的许多亚兆碱基损失和增益，并且在解析复杂 CN 变化的区域方面优于 CGH-BAC 阵列。
Genomic hybridization platforms, including BAC-CGH and genotyping arrays, have been used to estimate chromosome copy number (CN) in tumor samples by detecting the relative strength of genomic signal. The methods rely on the assumption that the predominant chromosomal background of the samples is diploid, an assumption that is frequently incorrect for tumor samples. In addition to generally greater resolution, an advantage of genotyping arrays over CGH arrays is the ability to detect signals from individual alleles, allowing estimation of loss-of-heterozygosity (LOH) and allelic ratios to enhance the interpretation of copy number alterations. Copy number events associated with LOH potentially have the same genetic consequences as deletions. We have utilized allelic ratios to detect patterns that are indicative of higher ploidy levels. An integrated analysis using allelic ratios, total signal and LOH indicates that many or most of the chromosomes from 24 glioblastoma tumors are in fact aneuploid. Some putative whole-chromosome losses actually represent trisomy, and many apparent sub-chromosomal losses are in fact relative losses against a triploid or tetraploid background. These results suggest a re-interpretation of previous findings based only on total signal ratios. One interesting observation is that many single or multiple-copy deletions occur at common putative tumor suppressor sites subsequent to chromosomal duplication; these losses do not necessarily result in LOH, but nonetheless occur in conspicuous patterns. The 500 K Mapping array was also capable of detecting many sub-mega base losses and gains that were overlooked by CGH-BAC arrays, and was superior to CGH-BAC arrays in resolving regions of complex CN variation.
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影响因子：
3.7
作者：
Lo, Ken C.;Rossi, Michael R.;Cowell, John K.
通讯作者：
Cowell, John K.
影响因子：
9.8
作者：
Friedman, J. M.;Baross, Agnes;Marra, Marco A.
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Marra, Marco A.
影响因子：
--
作者：
Cowell, JK;Matsui, SI;Nowak, NJ
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Nowak, NJ
影响因子：
11.2
作者：
Zhao, XJ;Li, C;Meyerson, M
通讯作者：
Meyerson, M
影响因子：
3.7
作者：
Lo, Ken C.;Rossi, Michael R.;Cowell, John K.
通讯作者：
Cowell, John K.