Hi-C detects genomic structural variants in peripheral blood of pediatric leukemia patients
- Claire Mallard1,2,7,
- Michael J. Johnston1,2,7,
- Anna Bobyn1,2,
- Ana Nikolic1,2,3,
- Bob Argiropoulos2,4,
- Jennifer A. Chan1,2,5,
- Gregory M.T. Guilcher1,2,6 and
- Marco Gallo1,2,3
- 1Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada;
- 2Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada;
- 3Department of Molecular Biology and Biochemistry, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada;
- 4Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada;
- 5Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada;
- 6Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada
- Corresponding authors: marco.gallo{at}ucalgary.ca; greg.guilcher{at}albertahealthservices.ca
Abstract
B-cell acute lymphoblastic leukemia (B-ALL) is often driven by chromosome translocations that result in recurrent and well-studied gene fusions. Currently, fluorescent in situ hybridization probes are used to detect candidate translocations in bone marrow samples from B-ALL patients. Recently Hi-C, a sequencing-based technique originally designed to reconstruct the three-dimensional architecture of the nuclear genome, was shown to effectively recognize structural variants. Here, we demonstrate that Hi-C can be used as a genome-wide assay to detect translocations and other structural variants of potential clinical interest. Structural variants were identified in both bone marrow and peripheral blood samples, including an ETV6–RUNX1 translocation present in one pediatric B-ALL patient. Our report provides proof of principle that Hi-C could be an effective strategy to globally detect driver structural variants in B-ALL peripheral blood specimens, reducing the need for invasive bone marrow biopsies and candidate-based clinical tests.
Footnotes
-
↵7 Co-first authors
-
[Supplemental material is available for this article.]
- Received October 22, 2021.
- Accepted November 22, 2021.
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
