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Unique Populations - 2019 CURE OM Symposium


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Dr. Jessica discusses the unique population and incidence of ocular melanoma diagnoses in Huntersville, NC.

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Unique Populations - 2019 CURE OM Symposium

  1. 1. Discover. Educate. Care. Lead. Genomic Analysis of Unique Uveal Melanoma (UM) Cases
  2. 2. Huntersville Project 22 reported cases of uveal melanoma in Huntersville, NC (15 females, 7 males) Consented 11 patients/family members for archival tissue collection Obtained 7 primary (6 enucleation, 1 FNA) and 2 metastatic (liver) tumor samples *Tissue missing or inadequate in other cases Whole genome sequencing (40X-80X) on 6 enucleation and 2 liver samples underway – anticipate results in May-June 2019
  3. 3. DNA Structure National Human Genome Research Institute DNA Structure | BioNinja
  4. 4. Whole Genome Sequencing (WGS) Figure out the cancer’s entire DNA sequence (all 6.4 billion letters)  Step 1: Separate tumor and adjacent normal tissue  Step 2: Extract DNA from tumor and matched normal tissue  Step 3: Whole genome sequencing (New York Genome Center) National Human Genome Research Institute corneaoptic nerve tumor
  5. 5. What can we learn from WGS? Whole genome sequencing Compare to public genome databases e.g. The Cancer Genome Atlas Compare to genomic data from other unique UM populations e.g. Auburn, AL Identify mutational signatures that may point to carcinogen exposure or specific mutational process More thorough evaluation of key driver mutations such as BAP1
  6. 6. Molecular landscape of uveal melanoma Field MG et al. Nature Communications 2018. Royer-Bertrand B et al. Am J Hum Genet 2016.
  7. 7. UV mutational signature Relationship between UV exposure and UM risk is unclear: welding identified as significant risk factor, but all forms of sun exposure were non-significant Characterized by CT transitions at pyrimidine dimers, including CCTT UV light triggers formation of covalent bonds between adjacent cytosine (C) or thymine (T) bases leads to DNA kinking and faulty replication Pyrimidine dimer Pyrimidine dimer Error-prone polymerase misreads template C to T mutation at site of adjacent pyrimidines
  8. 8. Tobacco mutational signature High prevalence of CA transversions on transcribed strand Polycyclic hydrocarbons and other carcinogens found in tobacco smoke interact with DNA to form bulky adducts on guanine (G) Principles of Cancer Biology, ©2006 Pearson Activated benzo(a)pyrene
  9. 9. 30 identified mutational signatures Signature 22. Aristolochic acid Signature 24. Aflatoxin B1 Signature 2. Activated APOBEC (possible viral etiology)