Glossary of Genes & Syndromes Feighanne Hathaway, MS LCGC Licensed Certified Genetic Counselor University Of Chicago Disclosures
▪ None
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
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