1. Faculty Disclosure In accordance with ACCME guidelines, any individual in a position to influence and/or control the content of this ASCP CME activity has disclosed all relevant financial relationships within the past 12 months with commercial interests that provide products and/or services related to the content of this CME activity. The individual below has responded that he/she has no relevant financial relationship(s) with commercial interest(s) to disclose: William K. Funkhouser, MD PhD

2. Molecular Pathology: The Future Wm. K. Funkhouser, MD PhD UNC Pathology & Lab Medicine

3. Our Future Pathology Practice will be: Citius - Faster Altius - Higher Fortius - Stronger

4. Citius - Faster

5. Faster Transfer from Discovery to Practice Galen to Harvey: Millennium Scurvy to citrus on ships: Century PCN to production: Decades HER2 amp, EGFR muts to Rx: Years ASCO meets annually….

6. Faster Technology Automation of chemistry Miniaturization of chemistry Computer analysis of data

7. Faster Risk Estimates For clinically unaffected individuals: Etiologic mutation screening for couples Etiologic mutation screening of relatives

8. Faster Diagnosis Molecular subtypes Specific translocations Germline etiologic mutations

9. Faster Prognosis Hemochromatosis A1AT deficiency Cystic fibrosis Medullary thyroid Ca in MEN2 MMR-defective colorectal Ca

10. Faster Prediction of Therapeutic Response Individual differences in drug metabolism “Druggable” mutant protein kinases ID of resistance mutations

11. Faster Detection of Copy Number Variation Gene Amplification Allelic Loss Multiplex testing ISH

12. Faster Translocation Detection Metaphase spreads Locus-specific probes

13. Faster Sequence Variation Detection Prenatal/Newborn screening HLA loci Germline vs. neoplasm muts Fusion partners Clonal Ig or TCR

14. Faster Epigenetic Testing Histone protein modification DNA promoter methylation Imprinting abnormalities

15. Faster RNA Abundance Cluster Analysis mRNAs µRNAs Their equilibria

16. Altius - Higher

17. Higher Complexity Multi-analyte tests Traits Statistics

18. Higher Confidence Risk prediction Diagnostic, prognostic, predictive Management guidance

19. Higher Productivity Timely reporting of accurate diagnoses with useful predictive data Prompt guidance of the treating clinician, particularly re. expensive targeted therapies

20. Fortius - Stronger

21. Stronger Associations Statistical associations Organizational associations

22. Stronger Opinions Education of lawyers, legislators, judges, and payors

23. Stronger Conclusions Better diagnostic reproducibility Better diagnostic accuracy Better outcome prediction Better management guidance

24. .

25. Going forward, Molecular Pathology will Improve our understanding of disease risk, etiology, pathogenesis, and outcomes Complement morphology Benefit our patients, our treating clinicians, and ourselves

26. Thanks to: Drs. Myers, Humphrey, DeYoung (ADASP Leaders) Drs. Eberhard, Sepulveda, and Pfeifer (Speakers) Drs. Gulley, Weck, Tsongalis, and Nowak (AMP) You, for participating in this ADASP meeting