Abstract Hispanic/Latino (HL) children have 50% higher risk of developing Acute Lymphoblastic Leukemia (B-ALL) than Non-Hispanic whites (NHW) and after correcting for socioeconomic factors, H/L children with B-ALL have 40% higher mortality than NHW. B-ALL in H/L children have a 2-fold greater rate of IKZF1 deletion (IKZF1-del) and a 4-fold greater rate of CRLF2 translocations, which are associated with chemotherapy resistance. This suggests that genetic background affects the pathogenesis and clinical course of B-ALL and is responsible for the worse outcome in H/L children with B-ALL. To address this problem, we created total of 42 patient-derived xenografts (PDXs) from H/L and NHW children with B-ALL and used a combination of whole genome sequencing (WGS) and optical genome mapping (OGM) to identify novel structural variants and oncogenic drivers of health disparity in pediatric leukemia in H/L children. We performed whole genome sequencing on all samples at an average depth of 40X and optical genome mapping at an average coverage of 273X (220X − 344X) on a Bionano optical mapping instrument. Results identified a large number of the novel deletions and translocations in both H/L and NHW children with B-ALL. Genomic location of the deletions showed enrichment at the boundaries of the known cancer driver genes in both populations, suggesting that deletions span regulatory elements that control gene transcription. Genome-wide distribution of deletions showed a distinct pattern in H/L compared with NHW children with B-ALL. Further analysis identified 6 deletions that were highly predominant in B-ALL in H/L children and are likely oncogenic drivers. Gene expression analysis showed strong upregulation of several oncogenic pathways, including PI3K/AKT/MTOR, and interferon signaling in H/L children with B-ALL samples. In conclusion. these results suggest that the use of whole genome sequencing in combination with optical mapping is an efficient strategy to identify genomic deletions and novel drivers of health disparity in pediatric leukemia in Hispanic/Latino children. Citation Format: Daniel Bogush, James Broach, Sinisa Dovat. The use of whole genome sequencing and optical genome mapping to identify novel drivers of health disparity in pediatric leukemia in Hispanic/Latino children abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B147.
Bogush et al. (Thu,) studied this question.