Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.

Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.
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DOI:
10.1371/journal.pone.0009983
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发表时间:
2010-04-08
期刊:
影响因子:
3.7
通讯作者:
Campbell IG
Campbell IG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ramakrishna M;Williams LH;Boyle SE;Bearfoot JL;Sridhar A;Speed TP;Gorringe KL;Campbell IG

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卵巢癌是一种以复杂的基因组重排为特征的疾病,但作为这些改变的靶点的大多数基因仍然未被识别。对这些靶基因进行分类将为疾病病因学提供有用的见解,并可能为开发新的诊断和治疗干预措施提供机会。高分辨率的全基因组拷贝数和匹配的表达数据,从68原发性上皮性卵巢癌的各种组织型进行整合,以确定最频繁的扩增与表达和拷贝数的最强相关性的区域中的基因。染色体3、7、8和20上的区域拷贝数增加最频繁(>40%的样品)。在这些区域内,当将具有增益的样品与没有增益的样品进行比较时,703/1370(51%)独特基因表达探针组差异表达。在这些差异表达的探针组中,有30%的探针组的表达量与拷贝数呈强正相关(r≥0.6)。我们还确定了21个高幅度拷贝数增加的区域,其中32个已知的蛋白质编码基因的表达和拷贝数之间表现出很强的正相关性。总的来说,我们的数据验证了先前已知的卵巢癌基因,如ERBB 2,并确定了新的潜在驱动因子,如MYNN,PUF 60和TPX 2。
Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (>40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r≥0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2.
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