JUN 20, 2019 12:00 PM PDT

NGS Target Enrichment Solutions to Drive Discovery in Precision Medicine Research

SPONSORED BY: Twist Bioscience
Speakers
  • Assistant Professor of Computational Biomedicine in Medicine, Weill Cornell Medical College
    Biography
      Dr. Duane Hassane is Director of Leukemia Genomics of the Englander Institute of Precision Medicine at Weill Cornell Medicine (WCM) and an Assistant Professor of Computational Biomedicine in Medicine. Prior to joining WCM, Dr. Hassane completed his postdoctoral training in AML stem cell research at the University of Rochester School of Medicine where he focused on precision drug discovery using genomic approaches. His research group focuses on AML detection, therapy, clonal hematopoiesis, and minimal residual disease (MRD). His research led to the development of several NGS based tests in oncology including the ExACT-2 platform for augmented pan-cancer exome analysis, a New York State approved myeloid malignancies test, and the forthcoming PreCISE-1 test for clonal hematopoiesis.
    • Senior Research Investigator, University of Pennsylvania
      Biography
        Dr. Guannan Wang is a trained molecular biologist and cancer genomics expert at University of Pennsylvania. She determines to dedicate her knowledge and skills to better understanding diseases and discovering new therapies, ultimately making positive impacts on patient care. Being a hardcore animal lover, Dr. Wang is now spearheading the effort to bring precision medicine into veterinary oncology, through personalized diagnosis and precision clinical trials in client-owned animals, ultimately improving care and treatment for our companion animals.

      Abstract:

      The long term goal of our collaborative effort is to bring precision medicine to the practice of veterinary oncology, using the wealth of genomic data gathered in human cancers as a roadmap.   We pioneered the concept of precision medicine in a common but deadly canine tumor, hemangiosarcoma (HSA), whose equivalent in human is angiosarcoma (AS), a rare yet highly fatal disease. We performed whole exome sequencing to investigate the mutation landscape of HSA and identified candidate driver mutations and therapeutic targets (Wang G, etc, 2017). Based on findings from exome sequencing and genomics data on homologous human disease (AS), I developed an amplicon-based targeted resequencing panel, HSA-panel, which allows genotyping of canine HSA at high coverage, high specificity and sensitivity and yet cost-effective. Together, the discovery sequencing and targeted panel sequencing identified candidate driver mutations in more than 90% patients’ samples, suggesting high diagnostic utility (Wang G, etc, unpublished). More importantly, the two most common driver mutations, present in more than 75% of HSA cases (Wang G, etc, unpublished), are great therapeutic targets suitable for pharmacological intervention, with specific inhibitors already in clinical use in humans. These findings offer us opportunities to perform clinical trials of targeted therapies in canine hemangiosarcoma, which may lead to novel and effective treatment options for canine disease, as well as to inform trial design for similar human disease. Our study in hemangiosarcoma serves as proof-of-concept to enable precision medicine in other canine cancers. To this end, I constructed a capture-based comprehensive canine cancer panel, which detects a wide range of mutations in 282 genes known to drive cancer development and covers a total target region of 1.4 mb in canine genome. Our goal is to identify driver mutations and clinically actionable biomarkers in all common canine cancers, to arm veterinary clinicians with better prognostic information, target therapeutic options, and markers to predict treatment response, ultimately enabling precision medicine in canine oncology. 
       

      The second part of this presentation will cover: 

      Somatic mutations accumulate in cells during normal aging. While most mutations are neutral, other mutations provide an advantage that can favor cell growth under certain conditions. In the blood, such non-neutral mutations drive clonal hematopoiesis (CH) in which many or most blood cells carry a common mutation that is detectable by next-generation sequencing. CH increases in prevalence as people age and is largely asymptomatic. However, data suggest that CH can be pro-inflammatory and thus may drive or catalyze a number of age-related disease processes - especially cardiovascular disease and hematologic cancers. Thus, the delineation of CH mutation patterns that predict disease risk has the potential to enable early detection and improvements in disease intervention. We describe CH mutation patterns that inform the risk and timing of acute myeloid leukemia (AML) as many as 17 years prior to diagnosis as well as the development of a new CH detection platform.



      Learning Objectives: 

      1. You will learn about the mutation landscape of a common yet deadly canine tumor, hemangiosarcoma, through whole exome sequencing and targeted panel resequencing
      2. You will learn about the identified candidate driver mutations and therapeutic targets in over 75% of cases


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