Chapter 15 - Sequencing a Single Circulating Tumor Cell for Genomic Assessment

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Advances in genomic technology and molecular diagnosis will allow the implementation of precision medicine in cancer patients in the near future. Such advances in knowledge and technologies have already enabled clinical scientists to dissect the genetic and molecular features linked to the initiation and progression of human malignancies, as well as the implementation of patient stratification for treatment and the prediction of therapeutic responses. Frequent re-biopsy of tumor tissues for real-time disease monitoring can be very challenging. Therefore, treatments are frequently based on the information generated from tissues obtained years ago at diagnosis, which does not represent the disease mutational profile and biologic characteristics at the later treatment stage. “Liquid biopsy”, which can be sampled frequently in a non- or minimally invasive manner, is gaining research focus for diagnostic and disease monitoring applications. Circulating tumor cells (CTCs), a major type of liquid biopsy, can serve as a rich resource of both cancer biological and genetic features to be used for frequent real-time monitoring of cancer development and progression as well as understanding cancer metastasis mechanisms. Single-cell CTC analysis offers a unique opportunity to uncover stochastic changes of individual cells as well as unknown regulatory pathways of cancer relapse or treatment resistance. Advances in both CTC harvesting and genomic sequencing technologies allowed researchers to perform genomic analysis of single CTCs. This chapter reviews the current state of technology for single CTC analysis, including CTC capture, whole-genome amplification for next-generation sequencing, and bioinformatics data analysis, with examples and prospects for research and clinical applications. Although single CTC sequencing remains out of reach for the majority of research and clinical laboratories due to the technical barriers, high cost, and lack of interpretation expertise, with the rapid technology advancements and annalistic tool development, single CTC sequencing will be widely used in the future both in the relevant research field and in clinical management of cancer patients.