138. Optical Genome Mapping workflow for identification and analysis of variants in Hematological Malignancies

Abstract

Clinical guidelines for hematological malignancies include structural variation (SV) analysis as part of the genetic analysis. Currently, this requires a combination of three cytogenetic technologies: karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA) to detect copy number variants, translocations, inversions, and other rearrangements. Next generation sequencing is also applied for small variant analysis but not successfully used for comprehensive SV analysis. Optical genome mapping (OGM) consolidates these cytogenetic techniques into a single assay capable of detecting all important genomic structural abnormalities. Furthermore, OGM detects cryptic SVs in a significant portion of cases and results in change interpretation of the biology underlying the malignancy in many cases. OGM is able to comprehensively detect variants down to 5% variant allele fraction from blood, bone marrow aspirates, and tumor biopsies, making it an ideal choice for oncology clinical research. Preanalytical and analytical steps require approximately 3-5 days from input sample to analyzed results. Dynamic filtering in OGM software can remove most polymorphic variants and prioritize relevant variants. In addition, it allows assignment of classification to variants and multiple user level review process (e.g. preliminary analysis by lab scientist and final review by lab supervisor). For example, an ALL case with t(9;22), deletion of CDKN2A, and whole chromosome gains of 4,6, and 10 can be easily visualized and then further examined and classified as needed. A variety of cases with hallmark abnormalities from various leukemias is presented here. This comprehensive technology allows for a quicker, more reliable output than traditional cytogenetic approaches.