MD Anderson癌症中心Nicholas E. Navin博士访谈

　　Oncology Frontier: Your lab at M.D. Anderson is working on some very advanced sequencing. Would you give us a brief introduction to it and to the single-cell sequencing tool and its purpose in clinical practice?

　　Dr. Navin: Most sequencing technologies to date have involved sequencing populations themselves， both tissue that you get from patients， usually from lumpectomies or surgeries， and the issue there is that it’s really a mixture of many different cell types and cells. It’s becoming clearer that there’s intra-tumor heterogeneity， which means that different tumor cells within one patient’s tumor can have different genomes and different mutations. And they’ll respond differently to therapy as well. And so that was really the motivation for us to start developing tools to be able to sequence smaller and smaller populations， and eventually we came to developing one of the first papers， that appeared in Nature， which was the first method to do single-cell sequencing.

　　And we use that to study triple-negative breast cancers， and we found that in some tumors， it looked like the copy number profiles， those are the amplifications and the deletions， are very clonal and very similar from cell to cell. But in other tumors， we could find multiple tumor populations present and that they’re all genetically related but that they have different oncegene and tumor suppressors in that tumor. And so these tools have been very useful in delineating the heterogeneity you see within a tumor.

　　So those are the methods we’ve been developing， and we’re just now starting to translate them into the clinic and find very important clinical applications where we think they can make a big impact on improving the lives of breast cancer patients.

　　《肿瘤瞭望》：您所在的M.D. Anderson实验室正在开展某些非常先进的测序工作。您能向我们简单介绍一下这项工作、单细胞测序工具及其在临床实践中的目的吗？

　　Navin博士：目前大多数测序技术涉及的对象是一个群体，通常为来源于经乳房肿瘤切除术和其他外科手术取得的患者组织，问题在于这些组织是由许多不同种类细胞组成的混合物。肿瘤内存在异质性，这一点已经越来越清楚，这意味着同一位患者肿瘤内的不同肿瘤细胞可拥有不同的基因组和不同的变异，对治疗产生不同的反应。这是我们着手开发能够针对更小群体进行测序的工具的动力。最终我们完成了第一篇论文，并发表在Nature杂志上，标志着第一种单细胞测序方法的诞生。

　　我们使用这种方法研究三阴性乳腺癌，发现在某些肿瘤中，不同细胞间的拷贝数特征，如扩增和缺失等高度克隆化，非常相似；但是在其他一些肿瘤中，存在多种肿瘤群体，它们存在遗传相关性，但是具有不同的致癌基因和抑癌基因。因此，这些工具在描绘肿瘤中的异质性时非常有用。

　　目前，我们正打算将开发的这些方法转化到临床，开发其临床应用价值，观察它是否能显著影响乳腺癌患者生存的改善。