LONG READ SEQUENCING in paediatric leukaemia demonstrates improved detection of clinically relevant structural variants, identifying alterations missed by standard diagnostic workflows and supporting more accurate disease classification.
Long Read Sequencing in Paediatric Leukaemia
Gene fusions are key drivers of paediatric leukaemia and arise from structural variants, yet current clinical workflows rely on multiple diagnostic methods that can increase both cost and turnaround time.
In this proof-of-concept study, investigators evaluated the use of long read sequencing in a cohort of 17 paediatric patients with leukaemia to determine its ability to detect clinically relevant structural variants.
The approach successfully identified all previously known clinically relevant structural variants detected through routine clinical testing (n=5/5), demonstrating full concordance with existing diagnostic methods.
These findings support the reliability of long read sequencing as a single assay capable of capturing key genomic alterations.
Detection Of Previously Missed Variants
Importantly, long read sequencing also identified additional clinically relevant structural variants that were not detected by routine approaches.
These findings enabled the classification of a leukaemia genetic subtype in four out of 12 patients who had not previously received a definitive subtype classification.
Among the newly detected alterations was an insertion event described as ins(11;10)(q23.3;p12p12), resulting in a KMT2A::MLLT10 gene fusion. This type of fusion is clinically significant and highlights the added sensitivity of long read sequencing in identifying complex structural rearrangements that may be overlooked using conventional multimodal workflows.
Implications For Clinical Practice
The results demonstrate the diagnostic potential of long read sequencing as a comprehensive tool for structural variant detection in paediatric leukaemia.
By consolidating multiple testing modalities into a single approach, this method may reduce analysis time and associated costs while improving diagnostic accuracy.
These findings support further investigation into the integration of long read sequencing into routine clinical practice, with the potential to enhance genetic classification and guide treatment decisions in paediatric leukaemia.
Reference
Lansdon LA et al. Proof-of-concept study for the detection of somatic structural variant driver alterations using HiFi long-read sequencing in a pediatric leukemia cohort. Npj Genomic Medicine. 2026; https://doi.org/10.1038/s41525-026-00560-5.
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