FEB 22, 2017 6:00 AM PST

Mate-pair next generation sequencing as a powerful clinical tool for the characterization of cancer

Speaker
  • Professor and Consultant, Department of Laboratory Medicine and Pathology, Mayo Clinic
    Biography
      David I Smith received his Ph.D. in Biochemistry from the University of Wisconsin in Madison in 1978 studying antibiotic resistance in bacteria. After doing post-doctoral work first at the Albert Einstein College of Medicine and then at the University of California, Irvine, he got his first faculty position at Wayne State University in 1985. In 1996 he joined the Mayo Clinic as a full Professor in the Department of Laboratory Medicine and Pathology. His laboratory studies the common fragile sites which are regions of profound genomic instability that are found in all individuals. His laboratory also studies the various ways that human
      papillomavirus is involved in the generation of different cancers. Dr. Smith is also the Chairman of the Technology Assessment Group for the Mayo Clinic Center for Individualized Medicine. The role of this group is to evaluate new technologies that could have a profound impact on basic research and its' clinical translation. The most exciting technology that has the greatest potential to change both research and clinical practice is next generation sequencing and Dr. Smith and his group have been using this technology to answer scientific questions. The advances in next generation sequencing over the past 10 years have been nothing
      short of incredible and it is now possible to generate terrabases of DNA sequence in a single run of a next generation sequencer. This technology can be utilized in a number of ways from characterizing just a few genes all the way to whole genome sequencing.

    Abstract

    Recent advances in DNA sequencing have now made it possible to characterize genomes, transcriptomes and even methylomes which is transforming both basic research and clinical practice. Whole genome sequencing (WGS) is a powerful tool to analyze molecular alterations that occur during the development of cancer, but there are a number of challenges to using WGS as a clinical tool. A practical alternative to WGS is the utilization of mate-pair next generation sequencing (MP-Seq) which can be done for a fraction of the cost of WGS. We have been using MP-Seq to characterize the different roles that human papillomavirus (HPV) plays in the development of different cancers. The cancer that we have been studying is oropharyngeal squamous cell carcinoma (OPSCC) as this cancer is increasingly caused by infection with HPV and there has been an epidemic increase in the incidence of this cancer. We utilized MP-Seq to analyze a group of HPV-positive OPSCCs. What we have found is that HPV is integrated into the genome of OPSCCs in only 30% of these cancers, which is quite distinct from what is observed in cervical cancer. In addition, we have found that the highly unstable common fragile sites and the large genes contained within these regions are hot-spots both for viral integrations and for other alterations in these cancers. Several large common fragile site genes are consistently altered in these cancers. MP-Seq can also determine genome-wide molecular alterations and these alterations can be utilized as cancer-specific markers for the detection of circulating tumor-free DNA from the blood of these patients. This could provide a powerful tool for the development of the liquid biopsy to monitor cancer-treatment of these patients. We will discuss how MP-Seq could thus become a powerful clinical tool for the characterization of genomic alterations in cancer and the development of the liquid biopsy.

    Learning Objective 1: Understand how MP-Seq can provide important information about genomic alterations in cancer

    Learning Objective 2: Learn about how HPV is involved in the development of different cancers

    Learning Objective 3: Learn about how MP-Seq can be a powerful tool to aid in the development of the liquid biopsy

     


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