Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Mol Oncol. 2010 Jun;4(3):267-83. doi: 10.1016/j.molonc.2010.04.010. Epub 2010 May 5.
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.
确定肿瘤进展的途径对于我们理解和治疗癌症至关重要。我们通常不会在患者疾病进展的多个时间点对其进行采样，因此我们的研究仅限于通过检查单个肿瘤样本来推断进展。尽管存在这种局限性，但推断进展是可行的，因为肿瘤基因组中包含了肿瘤形成过程中发生的突变的自然历史。重建进展谱系有两种方法：（1）肿瘤间比较，和（2）肿瘤内比较。肿瘤间方法包括从大量肿瘤样本中采集单个样本，并比较基因组的复杂性以识别早期和晚期突变。肿瘤内方法涉及从单个异质性肿瘤中采集多个样本，以比较发散的克隆并重建系统发育谱系。在这里，我们讨论了如何使用这些方法来解释当前的肿瘤进展模型。我们还比较了原发性和转移性拷贝数图谱的数据，以揭示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展将如何开启理解肿瘤异质性和进展的基本基础的新时代。
