Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer
Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer
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DOI：
10.1016/j.ccr.2005.08.003
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发表时间：
2005-09-01
期刊：
影响因子：
50.3
通讯作者：
Klein, CA
中科院分区：
文献类型：
--
作者：
Schardt, JA;Meyer, M;Klein, CA
已知人类乳腺癌中的染色体不稳定性发生在乳腺肿瘤显示侵袭的形态学迹象之前。我们在这里描述了一个意想不到的发现，一个肿瘤细胞群与正常核型分离的骨髓乳腺癌患者。通过分析相同的单细胞染色体畸变，亚染色体等位基因丢失和基因扩增，我们证实了它们的恶性起源，并描绘了乳腺癌进展过程中的基因组事件序列。根据基因组进展的轨迹，我们确定了一个极早期HER2扩增的患者亚群。由于早期变化最有可能被遗传不稳定的肿瘤细胞共享，因此播散性肿瘤细胞的遗传特征为选择患者进行靶向治疗提供了新的理论基础。
Chromosomal instability in human breast cancer is known to take place before mammary neoplasias display morphological signs of invasion. We describe here the unexpected finding of a tumor cell population with normal karyotypes isolated from bone marrow of breast cancer patients. By analyzing the same single cells for chromosomal aberrations, subchromosomal allelic losses, and gene amplifications, we confirmed their malignant origin and delineated the sequence of genomic events during breast cancer progression. On this trajectory of genomic progression, we identified a subpopulation of patients with very early HER2 amplification. Because early changes have the highest probability of being shared by genetically unstable tumor cells, the genetic characterization of disseminated tumor cells provides a novel rationale for selecting patients for targeted therapies.