To evaluate the utility of targeted adaptive sampling long-read sequencing (TAS-LRS) as a genome-profiling method in pediatric leukemia, addressing limitations of conventional methods.
Key Findings:
TAS-LRS successfully profiled all 28 patients with a turnaround time of approximately 72 hours, demonstrating its efficiency.
Identified 498 SNVs, 35 small indels, and 632 SVs, with 24 patients (85.7%) having determined genomic subtypes, highlighting its diagnostic potential.
TAS-LRS detected SVs, including cryptic fusions and large deletions, that were overlooked by clinical tests, underscoring its superiority.
CNV analyses revealed chromosome-level CNVs and focal CNVs not accurately described by G-banding, indicating comprehensive profiling capabilities.
Interpretation:
TAS-LRS demonstrates high efficiency in detecting genomic alterations in pediatric leukemia, surpassing limitations of conventional methods and offering significant clinical implications.
Limitations:
Comparison with short-read whole genome sequencing showed lower recall for certain variant types, which may affect clinical decision-making.
Some driver alterations were missed in tumor/normal-paired analysis due to quality classification, potentially impacting patient outcomes.
Conclusion:
TAS-LRS is a promising method for comprehensive genome profiling in pediatric leukemia, providing rapid and detailed insights into genomic alterations, with potential applications in clinical settings.
