Proof-of-concept study for the detection of somatic structural variant driver alterations using HiFi long-read sequencing in a pediatric leukemia cohort.

Creator(s)

• Lisa A. Lansdon
• Byunggil Yoo, Children's Mercy HospitalFollow
• Ayse Keskus
• Irina Pushel, Children's Mercy Kansas CityFollow
• Chengpeng Bi, Children's Mercy HospitalsFollow
• Tanveer Ahmad
• Asher Bryant
• Adam Walter, Children's Mercy HospitalFollow
• Margaret Gibson, Children's Mercy HospitalFollow
• Mary Rindler
• Weijie Li, Children's Mercy HospitalFollow
• Sahibu Sultan M Habeebu, Children's Mercy Hospital
• Linda D. Cooley
• John Herriges, Children's Mercy HospitalFollow
• Elena Repnikova, Children's Mercy HospitalFollow
• Lei Zhang, Children's Mercy HospitalFollow
• Keith August, Children's Mercy HospitalFollow
• Terrie Flatt, Children's Mercy HospitalFollow
• Alan S. Gamis, Children's Mercy HospitalFollow
• Erin M. Guest
• J Allyson Hays, Children's Mercy Kansas City
• Maxine Hetherington, Children's Mercy HospitalFollow
• Karen Lewing, Children's Mercy HospitalFollow
• Tomi Pastinen, Children's Mercy HospitalFollow
• Mikhail Kolmogorov
• Midhat S. Farooqi

Document Type

Article

Publication Date

6-8-2026

Identifier

DOI: 10.1038/s41525-026-00560-5; PMCID: PMC13243536

Abstract

Gene fusions are common primary drivers of pediatric leukemias and are the result of underlying structural variants (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 (n = 5/5) detected through routine clinical testing. This approach also identified crSVs that resulted in the classification of a leukemia genetic subtype for four additional patients (n = 4/12), such as an ins(11;10)(q23.3;p12p12) forming a KMT2A::MLLT10 fusion, that were missed by routine clinical approaches. 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.

Journal Title

NPJ Genom Med

Volume

11

Issue

1

PubMed ID

41957380

Comments

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Publisher's Link: https://www.nature.com/articles/s41525-026-00560-5

Recommended Citation

Lansdon LA, Yoo B, Keskus A, 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 Genom Med. 2026;11(1):32. Published 2026 Apr 9. doi:10.1038/s41525-026-00560-5