Abstract 2234: Detection of structural variation and analysis on HuKemia models by Using Bionano optical mapping

Abstract Background: Genomic Structural variation (SV) refer to abnormalities in chromosome structure, is a normal part of variation in the human genome. Now Genomics SVs are recognized as the largest source of interindividual genetic variation and are closely associated with oncogenesis. The ability to identify constitutive and low-allelic fraction SVs is crucial. Standard SV detection method include chromosome banding, fluorescence in situ hybridization (FISH), and array comparative genome hybridization (CGH), which are manually intensive and have trouble finding low-frequency mutations. In recent year, genome physical mapping technologies have received increasing attention and optical mapping-based methods can well-accomplish sufficient to detect large size SVs or SVs within repetitive regions. Lately, Bionano optical mapping technology rapidly expanded its applications in the detection of structural variations. As well known, Acute Leukemia show distinct patterns of genetic aberrations including chromosome translocations, mutations, and aneuploidies in genes responsible for cell cycle regulation and lymphoid cell development. Method: We use our liver cancer model LI6671 to establish the Bionano Saphyr Gen2 genome imaging platform. DNA >100kbp is extracted, “CTTAAG” sequences were labelled across the entire genome by using Direct-Label-Enzyme (DLE) and linearized through chips for visualizations. Saphyr was loaded, linearized, and imaged labeled DNA in repeated cycles. Assembly Algorithms covert collected DNA images into constructing consensus genome maps. And this assay platform will be used to comprehensively identify SVs for studying our 21 HuKemia models. Results: By using this fluorescence labels distribution patterns, we find different structure variants among genome. We used filtered data for genome map assembly and compared with human genome hg38 for SV detection. In LI6671, we found out 3952 SVs in LI667 including 1166 deletion, 2497 insertion, 101 duplication, 78 inversion breakpoints, 66 interchr. translocation breakpoints and intrachr. translocation. Oncogenesis related SVs, such as a ~13Kb heterozygous deletion at KCNQ1 region, EPC1::SP1 gene fusions have be founded. Conclusion: Saphyr is a comprehensive platform, can discover a broad range of Genomic SVs and further improves our understanding of Acute Lymphocytic Leukemia (ALL) and Acute Myelocytic Leukemia (AML). Citation Format: Xiaobo Chen, Huan Tian, Wubin Qian, Henry Q. Li, Sheng Guo. Detection of structural variation and analysis on HuKemia models by Using Bionano optical mapping [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2234.