Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Cold Spring Harb Mol Case Stud. 2022 Jan 10;8(1). doi: 10.1101/mcs.a006157. Print 2022 Jan.
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 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.
B 细胞急性淋巴细胞白血病 (B-ALL) 通常由染色体易位驱动，导致反复出现且研究充分的基因融合。目前，荧光原位杂交探针用于检测 B-ALL 患者骨髓样本中的候选易位。最近，Hi-C 技术（一种最初用于重建核基因组三维结构的测序技术）被证明可以有效地识别结构变体。在这里，我们证明 Hi-C 可作为一种全基因组检测方法，用于检测具有潜在临床意义的易位和其他结构变体。在骨髓和外周血样本中均鉴定到了结构变体，包括在一名儿科 B-ALL 患者中存在的易位。我们的报告提供了原理证明，即 Hi-C 可能是一种有效的策略，可用于全面检测 B-ALL 外周血样本中的驱动性结构变体，从而减少对侵入性骨髓活检和基于候选物的临床检测的需求。
