Successful classification of clinical pediatric leukemia genetic subtypes via structural variant detection using HiFi long-read sequencing
Lansdon, L. A.; Yoo, B.; Keskus, A.; Pushel, I.; Bi, C.; Ahmad, T.; Bryant, A.; Walter, A.; Gibson, M.; Rindler, M.; Li, W.; Habeebu, S. M.; Cooley, L. D.; Herriges, J.; Repnikova, E.; Zhang, L.; August, K. J.; Flatt, T. G.; Gamis, A. S.; Guest, E. M.; Hays, J. A.; Hetherington, M.; Lewing, K.; Pastinen, T.; Kolmogorov, M.; Farooqi, M. S.
Show abstract
Gene fusions are common primary drivers of pediatric leukemias and are the result of underlying structural variant (SVs). Current clinical workflows to detect such alterations rely on a multimodal approach, which often increases analysis time and overall cost of testing. In this study, we used long-read sequencing (lrSeq) as a proof-of-concept to determine whether clinically relevant (cr) SVs could be detected within a small (n = 17) pediatric leukemia cohort. We show that this methodology successfully determined all known crSVs detected through routine clinical testing. We also identified crSVs, such as an ins(11;10)(q23.3;p12p12) forming a KMT2A::MLLT10 fusion, missed by routine clinical approaches, resulting in the classification of leukemia genetic subtypes for four additional patients. This study demonstrates the diagnostic potential of lrSeq as an assay for SV detection in pediatric leukemia and supports lrSeq as a valuable tool for the accurate detection of crSVs.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia 93%
- Monosomy 7/del(7q) Cause Sensitivity to Inhibitors of Nicotinamide Phosphoribosyltransferase in Acute Myeloid Leukemia 93%
- Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities 92%
Similar papers in this journal
- Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms 95%
- The EAAT1 aspartate/glutamate transporter is dispensable for acute myeloid leukemia cell growth and response to therapy 92%
- NFAT are Essential and Redundant Actors for Leukemia Initiating Potential in T-cell Acute Lymphoblastic Leukemia 91%
Similar papers in this journal
- Clinical Impact of Panel Based Error Corrected Next Generation Sequencing versus Flow Cytometry to Detect Measurable Residual Disease (MRD) in Acute Myeloid Leukemia (AML) 94%
- Single-cell transcriptomics predicts relapse in MLL-rearranged acute lymphoblastic leukemia in infants 94%
- DEK::NUP214 acts as an XPO1-dependent transcriptional activator of essential leukemia genes 93%
Similar papers in this journal
- A high-throughput amplicon screen for somatic UBA1 variants in Cytopenic and Giant Cell Arteritis cohorts 90%
- Novel SYK variant causes enhanced SYK autophosphorylation and PI3K activation in an antibody-deficient patient 90%
- Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency 88%
Similar papers in this journal
- Genome-wide association analyses identify variants in IRF4 associated with acute myeloid leukemia and myelodysplastic syndrome susceptibility 93%
- Donor whole blood DNA methylation is not a strong predictor of acute graft versus host disease in unrelated donor allogeneic haematopoietic cell transplantation 92%
- The usage of human IGHJ genes follows a particular nonrandom selection: The recombination signal sequence affects the usage of human IGHJ genes 87%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.