26. Identification of novel genomic structural variations in Angiosarcoma by Optical Genome Mapping

Abstract

Angiosarcomas are malignant vascular tumors with a number of known molecular aberrations identified by standard technologies, such as FISH and next generation sequencing. However, potentially clinically significant large genomic aberrations, such as gene fusion, large amplification and deletions, may not be detectable by these technologies. To gain further insights into the genomic landscape of angiosarcoma, we performed optical genome mapping (OGM) of 3 primary human angiosarcoma cell lines. OGM analysis of these cells revealed multiple unique structural aberrations, including large insertions/deletions, inversions, duplications, inter-chromosomal and intra-chromosomal translocations. Further analysis showed a 354-Kb deletion in Plexin D1 gene locus that regulates the migration of endothelial cells and is required for normal development of the heart and vasculature; reciprocal t(4;9) translocation in UGT8 (UDP Glycosyltransferase 8) gene locus that is involved in biosynthesis of galactocerebrosidase; reciprocal t(6;22) translocation involving HIRA (Histone Cell Cycle Regulator) and EYS (Eyes Shut Homolog) gene loci; and 14 Mb inversion interrupting RYR2 (Ryanodine Receptor 2) and TAF1A (TATA-Box Binding Protein Associated Factor) gene loci. These findings demonstrate the utility of optical genome mapping as a new tool to uncover large genomic structural variations to better understand the molecular pathogenesis of malignant vascular tumors. Future studies are aimed to determine the biological significance of these structural variations in angiosarcoma.