1 / 18

Diagnostic Capabilities Beyond the Tumor Cell Genome

Diagnostic Capabilities Beyond the Tumor Cell Genome. Gregory J. Tsongalis, PhD, HCLD Professor of Pathology Director, Molecular Pathology Geisel School of Medicine at Dartmouth Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, NH

dore
Download Presentation

Diagnostic Capabilities Beyond the Tumor Cell Genome

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Diagnostic Capabilities Beyond the Tumor Cell Genome Gregory J. Tsongalis, PhD, HCLD Professor of Pathology Director, Molecular Pathology Geisel School of Medicine at Dartmouth Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, NH gregory.j.tsongalis@hitchcock.org

  2. Outline • Technology and Personalized Medicine • miRNAs • The liquid biopsy • Beyond that…….

  3. Technology and Therapeutics as Drivers of Medical Care Translational Research Therapeutics Technology Basic Science Clinical Medicine Clinical Laboratory Medicine

  4. The Genome Or The Human Karyotype

  5. Sequence by Synthesis Massively Parallel or Next Generation Sequencing at DHMC MiSeq PGM

  6. Personalized Medicine (A) Before crizotinib; (B) after 7 weeks of crizotinib. Shaw A T and Engelman J A JCO 2013;31:1105-1111

  7. Specificity(miRNAs as Biomarkers) Exportin 5 Dicer DGCR8 Drosha Pri-miRNA Pre-miRNA miRNA:miRNA* duplex Unwinding Nucleus RISC Cytoplasm Ribosome Translational Repression mRNA Cleavage C. L. Bartels and G.J. Tsongalis, Clin Chem, 2009;55: 623-631

  8. miRNA Profiling from Pancreatic FNAs 5 * 4 ** ** 5 16 24 FFPE matched tumor and normal HNSCC (6 laryngeal, 6 oral tongue) miRs: 21, 205, 12746 upregulated miRs:451, 125b downregulated Szafranska, Doleshal, Edmunds , Gordon , Luttges, Mundingv Barth Jr , Gutmann, Siriawinata , Pipas , Tannapfel , Korc, Hahn, Labourier , Tsongalis . Clin Chem 54(10):1716-1724, 2008. Hanoun, Delpu, Suriawinata, Bournet, Bureau, Selves, Tsongalis , Dufresne, Buscail, Cordelier, Torrisani. Clin Chem 56(7):1107-1118, 2010.

  9. Issues With The Tissues • Tumor tissue has inherent limitations • Tumor tissue is a single snapshot in time • Selection bias due to tumor heterogeneity • Invasive procedure

  10. A Huge Problem Resected Specimen Small Needle Core Biopsy Exhausted Block

  11. The Liquid Biopsy • Cell Free DNA (cfDNA) • Cells undergoing apoptosis or necrosis • Amount of cfDNA correlates with tumor staging and prognosis

  12. Xenograft Model Kerrington Smith, MD

  13. Promega PlexorHY

  14. Breath-based Diagnostics J. E. Hill, PhD Thayer School of Engineering at Dartmouth

  15. Breath-based Diagnostics

  16. Conclusions • Circulating nucleic acids become future biomarkers of choice • More advanced analysis of simpler specimens

  17. Molecular Pathology Laboratory and Translational Research Program Samantha Allen Paul Burchard Francine de Abreu, Ph.D. Leanne Cook Betty Dokus Amber Erskine Torrey Gallagher Arnold Hawk Joel Lefferts, Ph.D. Emmeline Liu Rebecca O’Meara Jason Peterson Elizabeth Reader Barbara Soares Heather Steinmetz Laura Tafe, M.D. Scott Turner, PhD Wendy Wells, M.D. Terri Wilson Eric York

More Related