A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines
A high-resolution integrated analysis of genetic and expression profiles of breast cancer cell lines
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DOI：
10.1007/s10549-008-0296-7
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发表时间：
2009-12-01
影响因子：
3.8
通讯作者：
Ashworth, Alan
中科院分区：
文献类型：
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作者：
Mackay, Alan;Tamber, Narinder;Ashworth, Alan
来源于乳腺癌患者的肿瘤细胞系是乳腺癌研究的基石之一。为了在遗传水平上表征乳腺癌细胞系，我们开发了一种全平铺路径细菌人工染色体（BAC）阵列收集，用于比较基因组杂交（aCGH）。这个aCGH BAC集合覆盖了整个人类基因组的98%，分辨率为40-60 kbp。我们将该平台与内部生产的17k cDNA微阵列一起使用，以表征24种乳腺癌细胞系的遗传和转录组学特征，以及来自非病变乳腺的细胞类型。我们证明乳腺癌细胞系具有再现原发性乳腺癌的基因组和转录组特征，并且可以可靠地细分为基底样亚群和管腔亚群。通过覆盖aCGH和转录组学数据，我们确定了753个基因的表达与拷贝数相关；该列表包含了许多在乳腺癌中反复扩增和过表达的癌基因（如HER2、MYC、CCND1和AURKA）。最后，我们证明，尽管乳腺癌细胞系具有通常在III级乳腺癌中发现的基因组特征（即1q、8q和20q的增加），基底样细胞系和腔细胞细胞系的特征是明显的基因组畸变。
Tumour cell lines derived from breast cancer patients constitute one of the cornerstones of breast cancer research. To characterise breast cancer cell lines at the genetic level, we have developed a full tiling path bacterial artificial chromosome (BAC) array collection for comparative genomic hybridisation (aCGH). This aCGH BAC collection covers 98% of the entire human genome at a resolution of 40-60 kbp. We have used this platform alongside an in-house produced 17 K cDNA microarray set to characterise the genetic and transcriptomic profiles of 24 breast cancer cell lines, as well as cell types derived from non-diseased breast. We demonstrate that breast cancer cell lines have genomic and transcriptomic features that recapitulate those of primary breast cancers and can be reliably subclassified into basal-like and luminal subgroups. By overlaying aCGH and transcriptomic data, we have identified 753 genes whose expression correlate with copy number; this list comprised numerous oncogenes recurrently amplified and overexpressed in breast cancer (e. g., HER2, MYC, CCND1 and AURKA). Finally, we demonstrate that although breast cancer cell lines have genomic features usually found in grade III breast cancers (i.e., gains of 1q, 8q and 20q), basal-like and luminal cell lines are characterised by distinct genomic aberrations.