Worldwide, lung cancer is the most commonly diagnosed form of cancer with a survival rate among the lowest. Somatic mutations (in the form of SNVs and InDels) and gene fusions account for the majority of clinically interpretable and actionable genomic alterations. Biomarkers for lung cancer and identification of molecular drug targets are also actively sought through protein analysis methodologies. Multi-analyte analysis of DNA, RNA, and protein is often hindered by limited amounts of FFPE-preserved specimens. When enough sample is available, each analyte is typically profiled on different instrument platforms, which requires complex workflows and specialized data analysis expertise. To provide a unified and simpler alternative, NanoString’s molecular barcoding technology has been adapted to permit simultaneous digital measurement of biologically-relevant targets that span DNA, RNA, and protein, known as 3D Biology™ technology. This approach has several advantages over other analytical methods. Direct, single-molecule digital counting allows detection over a broad dynamic range with high reproducibility, often >98% concordance between technical replicates. SNV probes enable sensitive and specific identification of ≤ 5% DNA mutant allele sequences from 5 ng of FFPE-extracted genomic DNA. Fusion transcripts are detected with 5’/3’ imbalance probes and toehold-mediated junction probes. Protein and phospho-protein expression is measured via DNA-labeled antibodies and a single antigen retrieval step. The 3D Biology workflow requires just two 5-10 µM sections of FFPE tissue; RNA/DNA extracted from one section and multiplex digital protein profiling from the second.
In this webinar, the speakers will discuss 3D Biology technology and the application of this novel approach in the study 75 lung cancer FFPE samples. These samples were assayed simultaneously with an SNV panel targeting 104 solid tumor somatic mutations in 25 genes, a lung cancer fusion gene panel targeting ALK, RET, ROS1 and NTRK1 transcripts, and a protein panel measuring 26 total and phospho-protein targets, including key members of the EGFR, PI3K, and MAPK signaling pathways. Combined with previous profiling of these samples utilizing 770-plex RNA profiling of key cancer pathways and 770-plex immune gene expression analysis, this multidimensional dataset points the way to a new generation of molecular biomarker-based signatures of disease and true multi-analyte analysis of limited FFPE samples.
Disclaimer: For Research Use Only. Not for use in diagnostic procedures.
Join the webinar to learn how 3D Biology Technology can enable your multi-analyte analysis of FFPE samples.
A. McGarry Houghton, MD, Associate Member, Clinical Research Division, Fred Hutchinson Cancer Research Center
Dr. Houghton is a pulmonologist and specializes in critical care, pulmonary complications of malignant disease, and lung cancer. His research focuses on the role of inflammatory cell derived proteinases in diseases occurring within the lungs. To date, this has included novel findings for many disease processes including lung cancer, acute lung injury, pulmonary infections, and pulmonary fibrosis. More recently, his focus has shifted to the tumor microenvironment. Dr. Houghton is currently investigating the role of innate immune cells within the tumor microenvironment in a comprehensive fashion.
Joseph M. Beechem, PhD, Senior Vice President of Research and Development, NanoString Technologies
Joseph M. Beechem, Ph.D. has served as Senior Vice President of Research and Development, since April 2012. Prior to joining our company, Dr. Beechem held various positions at Life Technologies, a publicly-traded biotechnology tools company, most recently as Vice President, Head of Advanced Sequencing and Head of Global Sequencing Chemistry, Biochemistry and Biophysics from January 2010 to April 2012. From December 2007 to December 2012, he served as Chief Technology Officer of Life Technologies. During his career at Life Technologies, he led the design and development of multiple genetic analysis technologies, the latest advanced SOLiD sequencing technology and the single molecule nano-DNA sequencing technology.
Prior to joining Life Technologies, Dr. Beechem was Chief Scientific Officer at Invitrogen, a publicly-traded biotechnology company that acquired Applied Biosystems in November 2008 to form Life Technologies, from August 2003 to December 2007 and Director of Biosciences at Molecular Probes, a biotechnology company acquired by Invitrogen in 2003, from August 2000 to August 2003. Prior to his industry experience, Dr. Beechem led an NIH-funded research laboratory for 11 years as a tenured associate professor at Vanderbilt University. He has authored or co-authored more than 100 peer-reviewed papers in diverse fields such as biomathematics, physics, chemistry, physiology, spectroscopy, diagnostics and biology. Dr. Beechem is also named on nearly 30 U.S. patents or patent applications and has served on a number of editorial and scientific advisory boards. He received a B.S. in Chemistry and Biology from Northern Kentucky University and a Ph.D. in Biophysics from The Johns Hopkins University.
Who Should Attend?
- Research Scientists
- Core Facility Managers
- Lab Directors/PI
- Post Doc Students
- Grad Students
- Biomarker discovery
- Biomarker validation
- Solid Tumor
- Translational Medicine
- Core Facility/Service Lab
NanoString Technologies (NASDAQ: NSTG) is a publicly held provider of life science tools for translational research and molecular diagnostics. The company’s technology enables a wide variety of basic research, translational medicine and in vitro diagnostics applications.
NanoString’s products are based on a novel digital molecular barcoding technology invented at the Institute for Systems Biology (ISB) in Seattle under direction of Dr. Leroy Hood. The company was founded in 2003 with an exclusive license to develop and market the technology. In 2008, NanoString launched its first commercial instrument system and began international sales operations with its first multiplexed assays for gene expression analysis. In 2010, the company launched new applications for the system to support microRNA analysis and copy number variation detection, and in 2013 launched Prosigna®, its first in vitro diagnostic product for prognosis of early stage breast cancer.
Organizations performing cancer research, biomarker validation and screening, and next-generation sequencing validation are rapidly adopting the nCounter® Analysis System. By providing simple, multiplexed digital profiling of single molecules, the NanoString platform represents a natural, digital downstream companion to next-generation sequencing and enables researchers to embark on studies that were previously inconceivable.
Leading researchers and institutions are finding that NanoString’s nCounter system provides the ideal platform on which to validate their discoveries and translate them into clinically useful diagnostic assays. The nCounter system is uniquely positioned to support translational research because it provides more reproducible results than methods requiring amplification, and generates high-quality data from the difficult sample types common in clinical research, including Formalin-Fixed Paraffin-Embedded (FFPE) tissues.
In addition to continuing to extend the applications for the nCounter system in the discovery, target validation and routine testing segments of the genomics research market, the company’s goal is to become the platform of choice for diagnostic testing based on multiplexed gene signatures that can be offered in hospitals and pathology laboratories worldwide, following appropriate regulatory approvals. These two synergistic areas of business focus provide researchers with a seamless transition from discovery to diagnostics.
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