Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
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DOI：
10.1186/1471-2407-10-460
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发表时间：
2010-08-27
期刊：
影响因子：
3.8
通讯作者：
Rothschild J
中科院分区：
文献类型：
--
作者：
Hawthorn L;Luce J;Stein L;Rothschild J
在解释乳腺癌样品产生的基因组谱数据中的一个主要挑战是识别驱动基因，其不同于不影响肿瘤发生的旁观者基因。评估转录组谱中改变的相对重要性的一种方法是将评估拷贝数改变（CNA）的变化的平行分析联合收割机组合。这种整合分析允许鉴定具有改变的表达的基因，所述基因映射在表现出拷贝数改变的特定染色体区域内，提供了鉴定“驱动基因”的机制方法。我们已经使用Affytek 250 K Mapping阵列对22个浸润性导管癌样本（IDC）进行了CNA的全基因组分析。使用Affytron U133 Plus2.0阵列对16个IDC样品进行转录物表达改变的分析。使用两个平台和整合的数据分析了14个IDC样本。我们还结合了杂合性缺失（洛）分析的数据，以确定在洛区域显示表达改变的基因。在1q21.3、6p21.3、7p11.2-p12.1、8q21.11和8q24.3鉴定了常见的染色体增益和扩增。在5p15.33处鉴定了一种新的扩增子。在1p36.22、8q23.3、11 p13、11 q23和22 q13发现了频繁的丢失。超过130个基因被鉴定为同时增加或减少表达，映射到这些区域的拷贝数改变。洛缺失分析显示3例肿瘤有17号染色体全染色体或p臂等位基因缺失。鉴定了定位于拷贝中性洛缺失区的基因。在Xp 24和Xp 25上检测到洛伴随拷贝丢失，并鉴定了定位到这些表达降低区域的基因。基因表达数据强调了肿瘤样本中的PPARα/RXRα激活途径下调。我们已经证明了使用高分辨率CGH和全基因组转录本分析的集成分析应用程序在IDC中检测驱动基因的实用性。高分辨率平台允许CNA的精细划分，基因表达谱分析提供了检测直接受CNA影响的基因的机制。这是第一个报告洛与基因表达集成在IDC使用高分辨率平台。
A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine parallel analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions which demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes'. We have performed whole genome analysis of CNAs using the Affymetrix 250K Mapping array on 22 infiltrating ductal carcinoma samples (IDCs). Analysis of transcript expression alterations was performed using the Affymetrix U133 Plus2.0 array on 16 IDC samples. Fourteen IDC samples were analyzed using both platforms and the data integrated. We also incorporated data from loss of heterozygosity (LOH) analysis to identify genes showing altered expression in LOH regions. Common chromosome gains and amplifications were identified at 1q21.3, 6p21.3, 7p11.2-p12.1, 8q21.11 and 8q24.3. A novel amplicon was identified at 5p15.33. Frequent losses were found at 1p36.22, 8q23.3, 11p13, 11q23, and 22q13. Over 130 genes were identified with concurrent increases or decreases in expression that mapped to these regions of copy number alterations. LOH analysis revealed three tumors with whole chromosome or p arm allelic loss of chromosome 17. Genes were identified that mapped to copy neutral LOH regions. LOH with accompanying copy loss was detected on Xp24 and Xp25 and genes mapping to these regions with decreased expression were identified. Gene expression data highlighted the PPARα/RXRα Activation Pathway as down-regulated in the tumor samples. We have demonstrated the utility of the application of integrated analysis using high resolution CGH and whole genome transcript analysis for detecting driver genes in IDC. The high resolution platform allowed a refined demarcation of CNAs and gene expression profiling provided a mechanism to detect genes directly impacted by the CNA. This is the first report of LOH integrated with gene expression in IDC using a high resolution platform.
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影响因子：
6.6
作者：
Stein, Leighton;Rothschild, Jenniffer;Hawthorn, Lesleyann
通讯作者：
Hawthorn, Lesleyann
DOI：
10.1158/1055-9965.epi-08-0821
发表时间：
2009-10
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Hoque MO;Prencipe M;Poeta ML;Barbano R;Valori VM;Copetti M;Gallo AP;Brait M;Maiello E;Apicella A;Rossiello R;Zito F;Stefania T;Paradiso A;Carella M;Dallapiccola B;Murgo R;Carosi I;Bisceglia M;Fazio VM;Sidransky D;Parrella P
通讯作者：
Parrella P
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
3.8
作者：
Cooke SL;Pole JC;Chin SF;Ellis IO;Caldas C;Edwards PA
通讯作者：
Edwards PA
影响因子：
3.7
作者：
Piao, Z;Malkhosyan, SR
通讯作者：
Malkhosyan, SR