文章：

通过配对末端测序（MPseq）表征儿童B淋巴母细胞白血病/淋巴瘤中的TCF3重排，发现复杂的基因组重排及一种新型TCF3/TEF基因融合

Characterization of TCF3 rearrangements in pediatric B-lymphoblastic leukemia/lymphoma by mate-pair sequencing (MPseq) identifies complex genomic rearrangements and a novel TCF3/TEF gene fusion

原文发布日期：2019-10-01

DOI: 10.1038/s41408-019-0239-z

类型: Article

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英文摘要：

The TCF3/PBX1 gene fusion is a recurrent genetic abnormality in pediatric B-lymphoblastic leukemia/lymphoma (B-ALL/LBL). While dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) probes can detect TCF3/PBX1 fusions, further characterization of atypical TCF3 FISH patterns as indicated by additional or diminished TCF3 signals is currently limited. Herein we describe the use of a next-generation sequencing assay, mate-pair sequencing (MPseq), to characterize typical and cryptic TCF3/PBX1 fusions and to identify TCF3 translocation partners based on results obtained from our laboratory-developed TCF3/PBX1 D-FISH probe set. MPseq was performed on 21 cases of pediatric B-ALL/LBL with either TCF3/PBX1 fusion, or no TCF3/PBX1 fusion but with additional or diminished TCF3 signals obtained by our PBX1/TCF3 D-FISH probe set. In addition, MPseq was performed on one pediatric B-ALL/LBL case with an apparently normal karyotype and abnormal TCF3 break-apart probe results. Of 22 specimens successfully evaluated by MPseq, 13 cases (59%) demonstrated TCF3/PBX1 fusion, including three cases with previously undescribed insertional rearrangements. The remaining nine cases (41%) harbored various TCF3 partners, including six cases with TCF3/ZNF384, and one case each with TCF3/HLF, TCF3/FLI1 and TCF3/TEF. Our results illustrate the power of MPseq to characterize TCF3 rearrangements with increased precision and accuracy over traditional cytogenetic methodologies.
 

摘要翻译： 

TCF3/PBX1基因融合是儿童B淋巴母细胞白血病/淋巴瘤（B-ALL/LBL）中常见的遗传学异常。虽然双色双融合荧光原位杂交（D-FISH）探针可检测TCF3/PBX1融合，但对TCF3信号增强或减弱所提示的非典型TCF3 FISH模式的进一步表征目前仍有限。本研究采用新一代测序技术——配对末端测序（MPseq），基于实验室自主研发的TCF3/PBX1 D-FISH探针组的检测结果，对典型性和隐匿性TCF3/PBX1融合进行表征，并鉴定TCF3易位伙伴。我们对21例儿童B-ALL/LBL样本进行MPseq分析，这些病例通过PBX1/TCF3 D-FISH探针组检测显示存在TCF3/PBX1融合，或无TCF3/PBX1融合但出现TCF3信号增强/减弱。此外，对1例核型显似正常但TCF3分离探针检测异常的儿童B-ALL/LBL病例也进行了MPseq分析。在成功完成MPseq检测的22例样本中，13例（59%）存在TCF3/PBX1融合，其中3例为既往未报道的插入性重排；其余9例（41%）涉及多种TCF3伙伴基因，包括6例TCF3/ZNF384融合，TCF3/HLF、TCF3/FLI1和TCF3/TEF融合各1例。我们的研究结果证明了MPseq在解析TCF3重排方面较传统细胞遗传学方法具有更高的精确度和准确性。

原文链接：

Characterization of TCF3 rearrangements in pediatric B-lymphoblastic leukemia/lymphoma by mate-pair sequencing (MPseq) identifies complex genomic rearrangements and a novel TCF3/TEF gene fusion