Real-time genomic characterization of pediatric acute leukemia using adaptive sampling
Year: 2024
Type: preprint
Abstract: hybridization (FISH), karyotype analysis, targeted PCR, and microarrays (Arber et al., 2016; Iacobucci & Mullighan, 2017; Narayanan & Weinberg, 2020). We investigated the feasibility of a comprehensive single-assay classification approach using long-read sequencing, with real-time genome target enrichment, to classify chromosomal abnormalities and structural variants characteristic of acute leukemia. We performed whole genome sequencing on DNA from diagnostic peripheral blood or bone marrow for 57 pediatric acute leukemia cases with diverse genomic subtypes. We demonstrated the characterization of known, clinically relevant karyotype abnormalities and structural variants concordant with standard-of-care clinical testing. Subtype-defining genomic alterations were identified in all cases following a maximum of forty-eight hours of sequencing. In 18 cases, we performed real-time analysis - concurrent with sequencing - and identified the driving alteration in as little as fifteen minutes (for karyotype) or up to six hours (for complex structural variants). Whole genome nanopore sequencing with adaptive sampling has the potential to provide genomic classification of acute leukemia specimens with reduced cost and turnaround time compared to the current standard of care.
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4403373565