Association between acquired uniparental disomy and homozygous mutations and HER2/ER/PR status in breast cancer.
Association between acquired uniparental disomy and homozygous mutations and HER2/ER/PR status in breast cancer.
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DOI：
10.1371/journal.pone.0015094
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发表时间：
2010-11-30
期刊：
影响因子：
3.7
通讯作者：
Amos CI
中科院分区：
文献类型：
--
作者：
Tuna M;Smid M;Zhu D;Martens JW;Amos CI
细胞信号网络中的遗传改变是癌症的标志，然而，缺乏发现它们的有效方法。最近发现了一种称为获得性单亲二体性（aUPD）的新型异常形式，可以精确定位各种癌症中突变基因的区域，从而确定下一代测序的区域。我们从Gene Expression Omnibus数据库中检索了大量基因组数据集，使用可以可靠检测aUPD的方法对乳腺肿瘤样本和细胞系中的aUPD进行全基因组分析。在52.29%的肿瘤样品中鉴定出aUPD。最常见的aUPD区域位于染色体2 q、3 p、5 q、9 p、9 q、10 q、11 q、13 q、14 q和17 q。我们评估了最常见的aUPD区域与HER 2/neu，ER和PR状态之间的任何相关性，并发现aUPD和三阴性（TN）乳腺癌复发区域之间存在统计学显著相关性。染色体17 q（VEZF 1、WNT 3）、3 p（SUMF 1、GRM 7）、9 p（MTAP、NFIB）和11 q（CASP 1、CASP 4、CASP 5）的aUPD是TN的预测因子。研究发现，与HER 2/neu阳性和/或ER或PR阳性病例相比，TN乳腺癌病例中aUPD的频率显着更高。此外，使用先前公布的突变数据，我们发现TP 53在该基因座具有aUPD的细胞系中同源突变。我们的结论是，aUPD是一种常见的和非随机的分子特征的乳腺癌，是最突出的三阴性病例。由于aUPD区域在主要病理亚型之间是不同的，特定的aUPD区域可以帮助乳腺癌的子分类。此外，我们以TP 53为例提供了统计学支持，表明鉴定aUPD区域可以是发现异常基因的有效方法。因此，我们得出结论，全基因组范围内的aUPD区域的纯合序列改变的分析可以提供有价值的见解乳腺肿瘤的发生。
Genetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing. We retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. aUPD was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using previously published mutation data, we found TP53 homozygously mutated in cell lines having aUPD in that locus. We conclude that aUPD is a common and non-random molecular feature of breast cancer that is most prominent in triple negative cases. As aUPD regions are different among the main pathological subtypes, specific aUPD regions may aid the sub-classification of breast cancer. In addition, we provide statistical support using TP53 as an example that identifying aUPD regions can be an effective approach in finding aberrant genes. We thus conclude that a genome-wide scale analysis of aUPD regions for homozygous sequence alterations can provide valuable insights into breast tumorigenesis.
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影响因子：
3.7
作者：
George RE;Attiyeh EF;Li S;Moreau LA;Neuberg D;Li C;Fox EA;Meyerson M;Diller L;Fortina P;Look AT;Maris JM
通讯作者：
Maris JM
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1002/ajmg.1320060207
发表时间：
1980-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
ENGEL, E
通讯作者：
ENGEL, E
影响因子：
11.2
作者：
Hu N;Wang C;Ng D;Clifford R;Yang HH;Tang ZZ;Wang QH;Han XY;Giffen C;Goldstein AM;Taylor PR;Lee MP
通讯作者：
Lee MP
影响因子：
2.6
作者：
Kralovics, R;Guan, YL;Prchal, JT
通讯作者：
Prchal, JT