Optical Genome Mapping for Comprehensive Assessment of Chromosomal Aberrations and Discovery of New Fusion Genes in Pediatric B-Acute Lymphoblastic Leukemia

SIMPLE SUMMARY: Acute lymphoblastic leukemia (ALL) is characterized by a large number of chromosomal, structural aberrations associated with risk stratification and treatment outcome. However, conventional karyotyping, FISH and PCR have many limitations in detecting chromosomal aberrations. The aim of our study was to assess the potential added value of optical genomic mapping (OGM) for identifying chromosomal aberrations. The chromosomal aberrations of 46 children with B-cell ALL were determined by OGM, and the results of OGM were compared with those of conventional techniques. We found that OGM could detect most clinically significant chromosomal aberrations, and that it has a strong ability to detect complex chromosomal aberrations and refine complex karyotypes. In addition, several novel fusion genes and single-gene mutations, associated with important clinical features, were also identified. Our results show that OGM is highly effective in identifying chromosomal aberrations and has important implications for risk stratification of ALL and the pathogenesis of leukemia. ABSTRACT: Purpose: To assess the potential added value of Optical Genomic Mapping (OGM) for identifying chromosomal aberrations. Methods: We utilized Optical Genomic Mapping (OGM) to determine chromosomal aberrations in 46 children with B-cell Acute lymphoblastic leukemia ALL (B-ALL) and compared the results of OGM with conventional technologies. Partial detection results were verified by WGS and PCR. Results: OGM showed a good concordance with conventional cytogenetic techniques in identifying the reproducible and pathologically significant genomic SVs. Two new fusion genes (LMNB1::PPP2R2B and TMEM272::KDM4B) were identified by OGM and verified by WGS and RT-PCR for the first time. OGM has a greater ability to detect complex chromosomal aberrations, refine complicated karyotypes, and identify more SVs. Several novel fusion genes and single-gene alterations, associated with definite or potential pathologic significance that had not been detected by traditional methods, were also identified. Conclusion: OGM addresses some of the limitations associated with conventional cytogenomic testing. This all-in-one process allows the detection of most major genomic risk markers in one test, which may have important meanings for the development of leukemia pathogenesis and targeted drugs.