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

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

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

Citius - Faster

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….

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

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

Faster Diagnosis Molecular subtypes Specific translocations Germline etiologic mutations

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

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

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

Faster Translocation Detection Metaphase spreads Locus-specific probes

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

Faster Epigenetic Testing Histone protein modification DNA promoter methylation Imprinting abnormalities

Faster RNA Abundance Cluster Analysis mRNAs µRNAs Their equilibria

Altius - Higher

Higher Complexity Multi-analyte tests Traits Statistics

Higher Confidence Risk prediction Diagnostic, prognostic, predictive Management guidance

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

Fortius - Stronger

Stronger Associations Statistical associations Organizational associations

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

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

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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

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