SAN DIEGO, Feb. 11, 2016 /PRNewswire/ -- Scientists from Silicon Biosystems Menarini today reported a groundbreaking cell-isolation method that opens the door to genetic analysis of previously preserved tumor samples that until now have been impossible to isolate with 100 percent purity. Utilizing the company's DEPArray™ technology to isolate specific tumor types in various stages of development, the researchers were able to characterize genetic variants of these cells that are clinically relevant, and may change the way tumor biopsies are characterized and diagnosed, laying the foundation for more precise cancer treatments. The study was reported today in the journal, Scientific Reports, a Nature publication.*
The DEPArray cell-isolation system optimizes high-throughput genetic analysis — so-called "next generation sequencing" (NGS) methods of molecular characterization — by adding digital precision to the process of sample preparation. "NGS has the potential to revolutionize clinical oncology by providing direct, actionable molecular information about tumor cells. Such information can be critical to developing personalized medical treatments against specific tumor types, as well as to stratify patients for appropriate clinical trials," explained Nicolo Manaresi, Ph.D., Chief Scientific Officer at Silicon Biosystems Menarini and the lead investigator in the study.
Overcoming FFPE and Tumor Heterogeneity
The power of NGS, however, is largely negated by FFPE — the de facto laboratory practice of preserving biopsy samples in formalin and embedding them with paraffin wax so they can be thin-sectioned for microscopic viewing. NGS is further compromised by "tumor heterogeneity" — the fact that tumor cells undergo dynamic cellular changes over time, constantly generating variant cell subpopulations that spread throughout the body. Moreover, heterogeneity inside the tumor cell population itself limits the possibility to identify drivers of tumor development, as low represented clones may actually be the ones responsible for more malignant traits.
Targeted cancer treatment requires monitoring these cell changes at the molecular level, especially those cells that have acquired drug resistance. Thus primary tumors become less relevant sources of molecular information, while monitoring of the evolution of specific cells in the course of the disease is critical for tailoring more precise patient treatment.
"Pre-analytical resolution of tumor heterogeneity is a major step forward for precision medicine," added Dr. Manaresi. "By enabling the addition of precise sample preparation to the NGS workflow, the DEPArray system brings precision medicine concepts such as personalized therapy, molecular monitoring of response to therapy, and liquid biopsy into the realm of practical possibility."
Unlocking the Power of Next Generation Sequencing for Tumor Analysis
Current available technology to solve sample heterogeneity, such as laser-capture microdissection and fluorescence-activated cell sorting (FACS) lack the accuracy and purity required for clinical use, and their power is often limited by the size and quality of the starting sample materials. The studied showed that the DEPArray cell-sorting and isolation technology, followed by NGS analysis, can reveal comprehensive genomic information from any FFPE sample, regardless of sample cellularity and size of the specimen. Moreover, the methodology informs a new model for conducting clinical biopsies of tumors, as well as for performing translational cancer research and the way new cancer drugs are developed and biomarkers discovered.
"The method we have developed, based on a pre-analytic digital cell separation from FFPE samples, achieves 100% purity of the sample, substantially reverting the DNA composition to a germline-like situation where NGS techniques can display all their power and reliability," said Dr. Manaresi. "Data analysis and interpretation of results are also drastically simplified and different classes of genetic alterations can be solved with unprecedented precision."
Selection and Isolation with Single-Cell Precision
Based on the principle of dielectrophoresis, which exploits the ability of a non-uniform electric field to move cells in a spatial gradient, the DEPArray platform provides precise image-based cell selection for identification and sorting of individual cells, or pools of cells, at 100% purity for further genetic analysis or culturing. The system enables investigators to recover desired live cells from a mixed tissue sample, such as FFPE samples, or from frozen tumor specimens, and cell cultures.
About Silicon Biosystems Menarini
Silicon Biosystems Menarini, based in San Diego, Calif. and Bologna, Italy, is a wholly owned subsidiary of The Menarini Group, a multinational pharmaceutical, biotechnology and diagnostics company headquartered in Florence, Italy, with a heritage of over 130 years and over 16,000 employees in more than 100 countries. The company manufactures and sells the DEPArray system, which enables researchers to automatically identify, quantify, and recover individual rare cells with single-cell precision. For more information visit http://www.siliconbiosystems.com.
* Bolognesi, C. et al. Digital Sorting of Pure Cell Populations Enables Unambiguous Genetic Analysis of Heterogeneous Formalin-Fixed Paraffin-Embedded Tumors by Next Generation Sequencing. Sci. Rep. 6, 20944; doi: 10.1038/srep20944 (2016).
SOURCE Silicon Biosystems Menarini