Novel patterns of genome rearrangement and their association with survival in breast cancer
Novel patterns of genome rearrangement and their association with survival in breast cancer
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DOI：
10.1101/gr.5460106
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发表时间：
2006-12-01
期刊：
影响因子：
7
通讯作者：
Zetterberg, Anders
中科院分区：
文献类型：
--
作者：
Hicks, James;Krasnitz, Alexander;Zetterberg, Anders
代表性寡核苷酸微阵列分析（ROMA）检测基因组扩增和缺失，其边界以近似50 kb的分辨率定义。我们使用这种技术检查了来自两项独立研究的243例乳腺肿瘤，这些研究提供了详细的临床数据。这项技术的高分辨率使我们能够识别二倍体肿瘤中基因组拷贝数变异的三种特征模式，并测量与患者生存率的相关性。其中一种模式的特征是多个紧密间隔的扩增子，或“风暴”，仅限于单个染色体臂。这些多重扩增与侵袭性疾病和较差的存活率高度相关，即使基因组的其余部分相对安静。一个选定的临床资料的子集的分析表明，一个简单的基因组计算，基因组变异的数量和接近的基础上，与原发性乳腺癌患者的总生存概率的生命表估计。基于这个样本，我们产生的工作假设，拷贝数分析可能提供有用的信息，使临床决策，特别是关于使用或不使用全身治疗（激素治疗，化疗），在管理可手术的原发性乳腺癌与表面上良好的预后，例如，小，淋巴结阴性，受体阳性二倍体病例。
Representational Oligonucleotide Microarray Analysis (ROMA) detects genomic amplifications and deletions with boundaries defined at a resolution of similar to 50 kb. We have used this technique to examine 243 breast tumors from two separate studies for which detailed clinical data were available. The very high resolution of this technology has enabled us to identify three characteristic patterns of genomic copy number variation in diploid tumors and to measure correlations with patient survival. One of these patterns is characterized by multiple closely spaced amplicons, or "firestorms," limited to single chromosome arms. These multiple amplifications are highly correlated with aggressive disease and poor survival even when the rest of the genome is relatively quiet. Analysis of a selected subset of clinical material suggests that a simple genomic calculation, based on the number and proximity of genomic alterations, correlates with life-table estimates of the probability of overall survival in patients with primary breast cancer. Based on this sample, we generate the working hypothesis that copy number profiling might provide information useful in making clinical decisions, especially regarding the use or not of systemic therapies (hormonal therapy, chemotherapy), in the management of operable primary breast cancer with ostensibly good prognosis, for example, small, node-negative, hormone-receptor-positive diploid cases.