Glossary of Genes & Syndromes Feighanne Hathaway, MS LCGC Licensed Certified Genetic Counselor University Of Chicago Disclosures ▪ None 2 What is Cancer Genetics 3 The Precision Medicine Initiative ▪ Disease treatment and prevention that incorporates individual genetic variation, environment and lifestyle ▪ Expand efforts in cancer genomics ▪ Support trials testing combinations of targeted therapies based on tumor’s molecular signature 4 Precision Medicine What is the best Why did I get this treatment for MY cancer? cancer? What is my chance to get What is the best cancer? screening for my risk? What is the Am I at risk for prognosis of MY severe side cancer? effects from this treatment? Precision Medicine Risk Pharmacogenomics New Therapies prediction • Drug dose of • Genetic defect • Begin colonoscopy medication at age 40 targeted therapy determined by for specific • Avoid high fat in drug metabolism disease diet genetic profile 6 All Cancer is Genetic Genetics Terminology ▪ Type of genetic testing Germline Somatic ▪ Possible genetic testing results Positive Negative Variant of uncertain significance ▪ Different Genes = Different Risks 8 Somatic vs Germline • Germline mutations = • germ cells (egg + sperm) • inherited • present from conception • present in every cell of the body • can be passed on to future generations • Somatic mutations = • Acquired • Arise by chance in any cell of the body • Cannot be passed down 9 Germline (inherited) vs. Tumor (somatic) Genetics Sporadic Cancer Hereditary Cancer 10 Genetics Terminology Nucleotide: DNA/RNA A, C, G, T (denoted as c.) Protein: amino acids ex: Cystein, Arginine (denoted as p.) 11 Each Individual has a unique DNA Sequence 12 Genetic Variants (Changes) ▪ Original: the gray cat ran down the hall ▪ Missense: the gray cat ran down the ball ▪ Insertion: the gray red cat ran down the hall ▪ Deletion: The gray ___ ran down the hall ▪ Duplication: The gray cat cat ran down the hall ▪ Nonsense: The gray 13 Does the variant harm the functioning of the gene/protein? 14 Possible Germline Genetic Test Results Pathogenic mutation Positiv identified Increased cancer e risk No mutations identified (benign variants/polymorphisms typically not reported) Negati Cancer risk based on personal/family history ve VU VUS S Cancer risk not yet known 15 Positive Results 16 Negative Results 17 VUS- Variant of Uncertain Significance 18 Not all Genes or Mutations Should Be Treated Equal Mutations in high risk Mutations in moderate genes are relatively risk genes can be more uncommon common . BRCA1 CDH1 ATM BRCA2 PALB2 CHEK2 TP53 19 Glossary of Syndromes 20 Syndromes identified in NCCN ▪ High-Penetrance Breast and Ovarian Cancer Susceptibility Genes (HBOC) ▪ Pancreatic Cancer Susceptibility Genes ▪ Li-Fraumeni Syndrome ▪ Cowden Syndrome/PTEN Hamartoma Tumor Syndrome ▪ Colorectal Cancer Syndromes 21 NCCN Guidelines Version 1.2020 22 NCCN Guidelines Version 1.2020 23 NCCN Guidelines Version 1.2020 24 NCCN Guidelines Version 1.2020 25 Thank You Contact Us 773-702-5163 [email protected] 26.