B-cell precursor (BCP) ALL carry a variety of classical V(D)J rearrangements as well as genomic fusions and translocations. Here, we assessed the value of genomic capture high-throughput sequencing (gc-HTS) in BCP ALL (n = 183) for the identification and implementation of targets for minimal residual disease (MRD) testing. For TRδ, a total of 300 clonal rearrangements were detected in 158 of 183 samples (86%). Beside clonal Vδ2-Dδ3, Dδ2-Dδ3, and Vδ2-Jα we identified a novel group of recurrent Dδ-Jα rearrangements, comprising Dδ2 or Dδ3 segments fused predominantly to Jα29. For IGH-JH, 329 clonal rearrangements were identified in 172 of 183 samples (94%) including novel types of V(D)J joining. Oligoclonality was found in ~1/3 (n = 57/183) of ALL samples. Genomic breakpoints were identified in 71 BCP-ALL. A distinct MRD high-risk subgroup of IGH-V(D)J-germline ALL revealed frequent deletions of IKZF1 (n = 7/11) and the presence of genomic fusions (n = 10/11). Quantitative measurement using genomic fusion breakpoints achieved equivalent results compared to conventional V(D)J-based MRD testing and could be advantageous upon persistence of a leukemic clone. Taken together, selective gc-HTS expands the spectrum of suitable MRD targets and allows for the identification of genomic fusions relevant to risk and treatment stratification in childhood ALL.

中文翻译：

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新的，复发性的基因组重排表征为儿童B细胞前体ALL中敏感的MRD靶标。

B细胞前体（BCP）ALL携带多种经典的V（D）J重排以及基因组融合和易位。在这里，我们评估了BCP ALL（n = 183）中的基因组捕获高通量测序（gc-HTS）对于鉴定和实施最小残留疾病（MRD）测试目标的价值。对于TRδ，在183个样品中的158个中检测到300个克隆重排（86％）。除了克隆的Vδ2-Dδ3，Dδ2-Dδ3和Vδ2-Jα外，我们还发现了一组新的周期性Dδ-Jα重排，包括主要与Jα29融合的Dδ2或Dδ3段。对于IGH-JH，在183个样品中的172个（94％）中鉴定出329个克隆重排，包括新型V（D）J连接。在所有样品的约1/3（n = 57/183）中发现了寡克隆现象。在71 BCP-ALL中鉴定了基因组断点。IGH-V（D）J-种系ALL的一个独特的MRD高风险亚组显示IKZF1的频繁缺失（n = 7/11）和基因组融合的存在（n = 10/11）。与传统的基于V（D）J的MRD测试相比，使用基因组融合断点进行的定量测量获得了等效的结果，并且在白血病克隆的持久性方面可能具有优势。总之，选择性gc-HTS扩大了合适的MRD靶标的范围，并允许鉴定与儿童ALL的风险和治疗分层有关的基因组融合。与传统的基于V（D）J的MRD测试相比，使用基因组融合断点进行的定量测量获得了等效的结果，并且在白血病克隆的持久性方面可能具有优势。总之，选择性gc-HTS扩大了合适的MRD靶标的范围，并允许鉴定与儿童ALL的风险和治疗分层有关的基因组融合。与传统的基于V（D）J的MRD测试相比，使用基因组融合断点进行的定量测量获得了等效的结果，并且在白血病克隆的持久性方面可能具有优势。总之，选择性gc-HTS扩大了合适的MRD靶标的范围，并允许鉴定与儿童ALL的风险和治疗分层有关的基因组融合。