Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers
Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers
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DOI：
10.1073/pnas.0808041105
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发表时间：
2008-10-21
影响因子：
11.1
通讯作者：
Velculescu, Victor E.
中科院分区：
文献类型：
--
作者：
Leary, Rebecca J.;Lin, Jimmy C.;Velculescu, Victor E.
我们已经使用能够可靠地检测纯合缺失和扩增的方法对乳腺和结肠直肠肿瘤中的拷贝数变化进行了全基因组分析。我们发现，主要拷贝数改变，删除所有拷贝或扩增到每个细胞至少12个拷贝，改变的基因数量平均为每个肿瘤17个。我们已经将这些数据与这些相同肿瘤类型中参考序列基因的先前突变分析相结合，并鉴定了受拷贝数变化和点改变影响的基因和细胞途径。富含遗传改变的途径包括控制细胞粘附、细胞内信号传导、DNA拓扑变化和细胞周期控制的途径。这些分析提供了全基因组范围内拷贝数和测序改变的综合视图，并确定了可能对癌症诊断和治疗有用的基因和途径。
we have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.