Tracing the tumor lineage.

Tracing the tumor lineage.
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DOI:
10.1016/j.molonc.2010.04.010
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发表时间:
2010-06
期刊:
影响因子:
6.6
通讯作者:
Hicks J
Hicks J
中科院分区:
医学2区
文献类型:
--
作者:
Navin NE;Hicks J

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明确肿瘤进展的途径对于我们对癌症的理解和治疗至关重要。我们不常规地在疾病进展的多个时间点对患者进行抽样,因此我们的研究仅限于通过检查单个肿瘤样本来推断其进展。尽管有这种局限性,推断进展是可能的,因为肿瘤基因组包含在肿瘤形成过程中发生的突变的自然历史。有两种重建进展谱系的方法:(1)肿瘤间比较和(2)肿瘤内比较。肿瘤间的方法包括从大量肿瘤集合中提取单个样本,并比较基因组的复杂性,以识别早期和晚期突变。肿瘤内方法包括从个体不同的肿瘤中提取多个样本,以比较不同的克隆并重建系统发生谱系。在这里,我们讨论如何使用这些方法来解释目前的肿瘤进展模型。我们还比较了原发癌和转移癌基因拷贝数分布的数据,以阐明乳腺癌进展的最后步骤。最后,我们讨论了单细胞基因组学的最新技术进步将如何预示着一个理解肿瘤异质性和进展的基本基础的新时代。
Defining the pathways through which tumors progress is critical to our understanding and treatment of cancer. We do not routinely sample patients at multiple time points during the progression of their disease, and thus our research is limited to inferring progression a posteriori from the examination of a single tumor sample. Despite this limitation, inferring progression is possible because the tumor genome contains a natural history of the mutations that occur during the formation of the tumor mass. There are two approaches to reconstructing a lineage of progression: (1) inter-tumor comparisons, and (2) intra-tumor comparisons. The inter-tumor approach consists of taking single samples from large collections of tumors and comparing the complexity of the genomes to identify early and late mutations. The intra-tumor approach involves taking multiple samples from individual heterogeneous tumors to compare divergent clones and reconstruct a phylogenetic lineage. Here we discuss how these approaches can be used to interpret the current models for tumor progression. We also compare data from primary and metastatic copy number profiles to shed light on the final steps of breast cancer progression. Finally, we discuss how recent technical advances in single cell genomics will herald a new era in understanding the fundamental basis of tumor heterogeneity and progression.
在412例患者的基于人群的队列中,乳腺癌的固有分子特征。
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