Inferring tumor progression from genomic heterogeneity
Inferring tumor progression from genomic heterogeneity
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DOI：
10.1101/gr.099622.109
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发表时间：
2010-01-01
期刊：
影响因子：
7
通讯作者：
Wigler, Michael
中科院分区：
文献类型：
--
作者：
Navin, Nicholas;Krasnitz, Alexander;Wigler, Michael
人类的癌症进展很难推断，因为我们不会在疾病的多个阶段对患者进行常规采样。然而，异质性乳腺肿瘤提供了一个独特的机会来研究人类肿瘤的进展，因为它们仍然包含证据的早期和中期亚群的形式的系统发育关系。我们开发了一种称为扇区倍性分析（SPP）的方法来研究乳腺肿瘤的克隆组成。SPP涉及宏观解剖肿瘤，通过DNA含量对基因组亚群进行流式分选，以及使用比较基因组杂交（CGH）分析基因组。乳腺癌显示两类基因组结构变异：（1）单基因组和（2）多基因组。单基因组肿瘤似乎包含一个单一的主要克隆亚群，具有高度稳定的染色体结构。多基因组肿瘤包含多个克隆肿瘤亚群，其可以占据相同的扇区或单独的解剖位置。在多基因组肿瘤中，我们发现异质性可以归因于一些克隆亚群，而不是一系列逐渐的中间体。通过比较来自不同解剖位置的多个亚群，我们推断了癌症进展的途径和肿瘤生长的组织。
Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.