1 / 14

Genomics-Based Personalized Healthcare

Genomics-Based Personalized Healthcare. Presented by: Charis Eng, MD, PhD - Chair & Director Genomic Medicine Institute Director Center for Personalized Genetic Healthcare. Example Problem at Hand. Why the Different Responses to Same Treatment?. Insert Text. Asthma Attack Stopped.

shlomo
Download Presentation

Genomics-Based Personalized Healthcare

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. Genomics-Based Personalized Healthcare Presented by: • Charis Eng, MD, PhD • - Chair & Director • Genomic Medicine Institute • Director • Center for Personalized Genetic Healthcare

  2. Example Problem at Hand Why the Different Responses to Same Treatment? Insert Text Asthma Attack Stopped Bottom Child Has a Genetic Variant In B-Adrenergic Receptor Gene B-Adrenergic Inhalers Both Have Asthmatic Attacks Dead

  3. Breast Conserving Surgery Adjuvant Chemotherapy Breast Conserving Surgery Adjuvant Chemotherapy Example Problem at Hand Why the difference? “Normal” Gene Cured Early Stage Breast Cancer “Altered” Gene Dies of Ovarian Cancer 10 Years Later

  4. Who is at risk for which disease(s)?

  5. Based on Objective Genomic or Genetic Data: • WHO is at risk of developing disease(s)? • Potentially Entire Population • Personalized risk assessment • WHAT can we do about genomic risk? • Personalized risk management • Personalized preventive and curative measures? • WHEN is age (range) of highest risk? • WHERE: Can surveillance be organ-specific? • WHY and HOW? • Patient-Oriented Genomics/Genetics Research

  6. “Sporadic” “Environmental Exposure” “Bad Luck” A BIG RED DOG. Variants: THE BIG RED GOD. “Some Genetic Component” “Familial Clustering” High Penetrance Disease Susceptibility Gene(s) THE BIR EDD OG. Mutated Genes: THE BIG R. Genetic Load for Any Disease Emerging Dogma Current Dogma Normal Gene: THE BIG RED DOG.

  7. High Penetrance Disease Susceptibility Gene(s) High Penetrance Breast Cancer Susceptibility Genes BRCA1 BRCA2 PTEN TP53 LKB1 Mutation in Gene > High Likelihood of Developing Breast and Other Component Cancers

  8. Common Low Penetrance Variants Associated with Breast Cancer Cases Controls 100 4,000 THE BIG RED DOG. 70 70 THE BIG RED RIG. 1,500 10 THE BIG RED GOD. 55 70 WOW BIG RED DOG. 2,500 25 A BIG RED DOG. Genome-Wide Association Studies A BIG RED DOG. FGFR2 TNRC9 MAP3K1 LSP1 CASP8 Variants: Easton DF et al Nature 2007 Cox A et al Nature Genet 2007 Pharoah et al PloS Genet 2007 THE BIG RED GOD.

  9. Low Penetrance Variants in Various Genes Associated with Various Diseases*That Have Replicated (<5% of All Association Studies)*That Give Risks with OR >1.15 (low level risk) • Subsets of: • Breast Cancer • Prostate Cancer • Diabetes Mellitus Type 2 • Obesity • Coronary Heart Disease • Crohn Disease • Others

  10. N LOH Ep. Somatic Genetic Alterations in Sporadic Carcinomas • Epithelial component of carcinomas believed to be the neoplastic component • Pathologists measure invasion by whether the neoplastic epithelial cells invade membrane • Genetic alterations believed in epithelium

  11. Normal Normal Tissue Ep St TP53 Exon 2 Mutation TP53 Exon 6 Mutation Somatic TP53 and Other Gene Mutations in Stroma of Breast Carcinomas Kurose et al Nature Genet 2002, Fukino et al JAMA 2007

  12. St TP53 Mutation Stromal (Not Epithelial) Genomic Alterations Associated with Tumor Aggressiveness and Metastases in Breast and Head and Neck Cancers Weber et al JAMA 2007, Fukino et al JAMA 2007, Patocs et al N Engl J Med (almost in press)

  13. Low Risk Breast Cancer Or Any Disease ACS Guidelines General Population High Risk Receive Gene Test Results Post-Test Counseling Test Negative Center for Personalized Genetic Healthcare Personalized Genetic Health Assessment and Management 2007 Is it hereditary or sporadic? Personal & Family History Age at Onset Other Types of Cancer One or More Organs Pedigree Drawing Epidemiology says 10-15% caused by high penetrance mutant genes, BUT which 10-15%? Pre-Test Genetic Counseling Genetic Testing Risk Management Screening Prophylactic Surgery Test Positive

  14. Prioritization & Testing of Known High Penetrance Cancer Genes in Setting of Genetic Counseling Multiple Generation Pedigree For Cancer Genetic Risk Assessment Clinical Screening, Preventative Measures, Behavior Modification Select Multi-Agent Targeted Therapy With >99% Likelihood of Durable Response & <1% Likelihood Of Adverse Effects Germline Variant Profling Biopsy of Cancer Somatic Genomic Profiling of Cancer Epithelium & Stroma Histopathology Genomics-Based Personalized Healthcare for Cancer 2008-09 Multidisciplinary Cancer Consult Including Genomic Medicine And Genetic Counseling

More Related