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OncoScape:通过基因组数据融合探索癌症变异全景

OncoScape: Exploring the cancer aberration landscape by genomic data fusion.

机构信息

Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Research IT, Netherlands Cancer Institute, Amsterdam, The Netherlands.

出版信息

Sci Rep. 2016 Jun 20;6:28103. doi: 10.1038/srep28103.

Abstract

Although large-scale efforts for molecular profiling of cancer samples provide multiple data types for many samples, most approaches for finding candidate cancer genes rely on somatic mutations and DNA copy number only. We present a new method, OncoScape, which exploits five complementary data types across 11 cancer types to identify new candidate cancer genes. We find many rarely mutated genes that are strongly affected by other aberrations. We retrieve the majority of known cancer genes but also new candidates such as STK31 and MSRA with very high confidence. Several genes show a dual oncogene- and tumor suppressor-like behavior depending on the tumor type. Most notably, the well-known tumor suppressor RB1 shows strong oncogene-like signal in colon cancer. We applied OncoScape to cell lines representing ten cancer types, providing the most comprehensive comparison of aberrations in cell lines and tumor samples to date. This revealed that glioblastoma, breast and colon cancer show strong similarity between cell lines and tumors, while head and neck squamous cell carcinoma and bladder cancer, exhibit very little similarity between cell lines and tumors. To facilitate exploration of the cancer aberration landscape, we created a web portal enabling interactive analysis of OncoScape results (http://ccb.nki.nl/software/oncoscape).

摘要

尽管大规模的癌症样本分子谱分析为许多样本提供了多种数据类型,但大多数寻找候选癌症基因的方法仅依赖于体细胞突变和 DNA 拷贝数。我们提出了一种新的方法 OncoScape,它利用了 11 种癌症类型中的五种互补数据类型来识别新的候选癌症基因。我们发现了许多很少发生突变但受其他异常影响很大的基因。我们检索到了大多数已知的癌症基因,但也检索到了 STK31 和 MSRA 等新的候选基因,其可信度非常高。一些基因根据肿瘤类型表现出双重癌基因和肿瘤抑制基因样行为。值得注意的是,著名的肿瘤抑制基因 RB1 在结肠癌中表现出强烈的癌基因样信号。我们将 OncoScape 应用于代表十种癌症类型的细胞系,提供了迄今为止细胞系和肿瘤样本中异常情况的最全面比较。这表明胶质母细胞瘤、乳腺癌和结肠癌在细胞系和肿瘤之间具有很强的相似性,而头颈部鳞状细胞癌和膀胱癌在细胞系和肿瘤之间则表现出很少的相似性。为了便于探索癌症异常景观,我们创建了一个网络门户,使 OncoScape 结果的交互式分析成为可能 (http://ccb.nki.nl/software/oncoscape)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d1f/4913322/19473ec9788b/srep28103-f1.jpg

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