Guidelines from WHO, NCCN and others, for the genetic analysis of hematological malignancies included structural variation analysis. Traditionally, this has relied on a combination of three cytogenetic technologies for structural variation analysis: karyotyping, FISH, and microarray, are used to detect copy number variants, translocations, inversions. Next generation sequencing is also applied for mutation analysis but has not been successful for structural variation analysis. These traditional methods have many very manual aspects and require extensive expertise. Optical genome mapping (OGM) consolidates assays into a single laboratory assay in which the output provides the visualization of structural and copy number variants at one time. OGM is able to comprehensively detect structural variations genome wide down to 5% variant allele fraction for CNVs, inversions, and translocations from blood and bone marrow aspirates making it an attractive choice for hematologic malignancy genomic analysis. Preanalytical and analytical steps require approximately 4-5 days from sample to processed data with structural variation calls. Dynamic filtering in the user interface can be configured to remove most polymorphic variants and prioritize relevant variants. In addition, the OGM graphical user interface software, Bionano Access 1.7, allows for the user to assign classification/relevance to the variants for each case. For example, an ALL sample with t(9;22), deletion of CDKN2A, and whole chromosome gains of 4,6, and 10 can be easily visualized with the Circos plot and, then, can be further examined and annotated as needed. A second analyst can repeat the process blind to the first analysis and a supervisor can adjudicate the classifications. A variety of cases with hallmark abnormalities from various leukemias will be presented with the filtering and prioritization workflow used to derive them. This comprehensive technology allows for a quicker, more reliable output than traditional cytogenetic approaches.

Citation Format: Jennifer Hauenstein, Andy Pang, Alka Chaubey, Alex Hastie. Optical genome mapping workflow for identification and annotation of variants in hematological diseases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2931.