PRESENTATION ABSTRACTS
cat pattern. This work reveals genes and signaling pathways that underlie pattern variation in the domestic and wild felids and illustrates how forward genetic and functional genomic approaches can be synergistically applied to identify when, where, and how color patterns form.
#26 Role of PIK3CA mutations in Chromatin Accessibility and Transcriptional Program in Canine Hemangiosarcoma Emma Kozurek 1,2,3 ,Zhiyan Silvia Liu 4 , Hai Dang Nguyen 3,4 , Jong Hyuk Kim 5,6 jkim19@ufl.edu 1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA, 2 Animal Cancer Care and Research Program, University of Minnesota, St. Paul, MN, USA, 3 Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA 4 Department of Pharma- cology, Medical School, University of Minnesota, Minneapolis, MN, USA, 5 Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA, 6 Intelligent Comparative Oncology Lab, University of Florida, Gainesville, FL, USA Hemangiosarcomas are genomically complex, soft tissue sarcomas which are prevalent in domestic dogs. Despite the genomic complexity, hemangiosarcomas share a histological morphology that consists of disorganized, malignant vessel-forming cells. This pathognomonic feature may be established by a regulatory machinery that activate convergent signaling pathways for malignant vasculogenesis. PIK3CA mutations are identified in canine hemangiosarcomas, and PI3K pathway is broadly activated across these tumors. In this study, we aimed to determine if PIK3CA mutations establish distinct molecular program to regulate chromatin accessibility and subsequent tran- scriptional activity in hemangiosarcoma. We first induced homozygous PIK3CA H1047R hotspot mutations in canine hemangiosarcoma cells using CRIPSR/Cas9. Two mutant cell clones and wild-type clone were obtained by single cell clonal selection. In addition to functional characteriza- tion, ATAC-seq (n=12), bulk RNA-seq (n=36), and 10x single cell RNA-seq (n=8) data were generated from PIK3CA-mutant and wild-type hemangiosarcoma cells with treatment of PI3K inhibitors. Our gene expression profiling data revealed that PIK3CA mutant cells enriched distinct gene signatures associated with DNA damage and immune regulation. PI3KCA mutant hemangiosarcoma cells were more susceptible to DNA damage than wild-type cells. We further identified single cell subsets associated with the enriched pro-angiogenic and inflammatory genes in the mutant hemangiosar- coma cells by single cell genomics data. Ongoing work is to identify open and closed chromatin regions associated with transcription factors that activate downstream signaling pathways induced by PIK3CA mutations.
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