文章：

表征新型、复发性基因组重排作为儿童B细胞前体ALL的敏感MRD靶标

Characterization of novel, recurrent genomic rearrangements as sensitive MRD targets in childhood B-cell precursor ALL

原文发布日期：2019-11-29

DOI: 10.1038/s41408-019-0257-x

类型: Article

开放获取: 是

英文摘要：

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.
 

摘要翻译： 

B细胞前体（BCP）急性淋巴细胞白血病携带多种经典的V(D)J重排以及基因组融合和易位。本研究通过基因组捕获高通量测序技术对183例BCP-ALL患者进行分析，旨在评估该技术在识别和实施微小残留病检测靶标方面的价值。在TRδ基因方面，183例样本中有158例检测到300个克隆性重排。除经典的Vδ2-Dδ3、Dδ2-Dδ3和Vδ2-Jα重排外，我们还发现了一组新型复发性Dδ-Jα重排，主要表现为Dδ2或Dδ3片段与Jα29的融合。在IGH-JH基因方面，183例样本中有172例鉴定出329个克隆性重排。约三分之一样本存在寡克隆性。在71例BCP-ALL中识别出基因组断点。研究发现IGH-V(D)J种系型ALL这一特殊高危亚型普遍存在IKZF1缺失和基因组融合现象。基于基因组融合断点的定量检测与传统V(D)J重排检测结果高度一致，且在白血病克隆持续存在时更具优势。综上，选择性基因组捕获高通量测序可扩展微小残留病检测靶标范围，并能识别与儿童ALL风险分层和治疗策略相关的基因组融合事件。

原文链接：

Characterization of novel, recurrent genomic rearrangements as sensitive MRD targets in childhood B-cell precursor ALL