Clinical OMICS

MAY-JUN 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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www.clinicalomics.com May/June 2017 Clinical OMICs 21 may provide better opportunities for creating combinatorial therapies." Around the same time Dr. Navin was working on sin- gle-cell genome sequencing, other researchers were also working on developing techniques for sequencing RNA from single cells (transcriptomics). By sequencing the RNA (RNA-seq) present in single can- cer cells, it is possible to find out what type of cell it is or what signals it is producing or receiving from its neighbors. "This provides a whole new level of understanding of the biology of a tumor," Dr. Robson said. Dr. Robson and many other cancer researchers are now using these techniques to investigate tumor heterogeneity and are moving closer to developing better diagnostic and prognostic tools, as well as more targeted therapies, for use in the clinic. Little Is More Single-cell sequencing has a number of attractions for can- cer researchers over more traditional "bulk" sequencing techniques. "Each tumor is composed of a very diverse set of cells, including both cancer cells with distinct genetic and pheno- typic features, and various noncancer cells, such as immune and stromal cells," said Itay Tirosh, Ph.D., a postdoctoral fellow at the Broad Institute in Cambridge, MA, who spe- cializes in single-cell analysis. "Without single cell methods, we are averaging across all of their cells, but single-cell methods allow us to accurately profile the tumor and distinguish its various components," he explained. "If you look at RNA expression, many genes are expressed in almost every cancer cell. So if the level is high in one and low in the other you would never know from the bulk RNA sequencing," commented Nir Hacohen, Ph.D., director of the Massachusetts General Hospital Center for Cancer Immunotherapy. "With bulk DNA sequencing we have some chance because there are typically only two copies of the gene, so you can make assumptions about the number of copies, but with RNA we have no idea, it's a random number." Another advantage of single-cell sequencing is that it can help identify the sometimes crucial influence of small sub- populations of cells that might otherwise be missed using bulk techniques. "For example, tumors may respond to a drug treatment (continued on next page) Images from the NCI Cancer Close Up collections: left: Human colon cancer cells with the cell nuclei stained red and the protein E-cadherin stained green created by Urbain Weyemi, Christophe E. Redon and William M. Bonner; middle: A cluster of slow-cycling (AKT-low/Hes 1-high) breast cancer cells (red) within a human ER+ primary breast tumor (cell nuclei in blue; rapidly cycling, AKT-high, cancer cells in green), created by Sheheryar Kabraji and Sridhar Ramaswamy; right: A single gene called Pem (purple) has been localized using fluorescence in situ hybridization. DNA is stained blue; the cell cytoplasm is stained green, created by Tom Misteli. National Cancer Institute

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