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.,Blood Cancer Journal

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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.
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2019-10-01 , DOI: 10.1038/s41408-019-0239-z
Ross A Rowsey ₁ , Stephanie A Smoley ₁ , Cynthia M Williamson ₁ , George Vasmatzis ₂ , James B Smadbeck ₂ , Yi Ning ₃ , Patricia T Greipp ₁ , Nicole L Hoppman ₁ , Linda B Baughn ₁ , Rhett P Ketterling ₁ , Jess F Peterson ₁

Affiliation

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.

中文翻译：

小儿B淋巴细胞白血病/淋巴瘤中的TCF3重排通过伴侣对测序（MPseq）的特征鉴定了复杂的基因组重排和新型TCF3 / TEF基因融合。

TCF3 / PBX1基因融合是小儿B淋巴细胞白血病/淋巴瘤（B-ALL / LBL）的复发性遗传异常。虽然双色，双融合荧光原位杂交（D-FISH）探针可以检测TCF3 / PBX1融合，但目前还难以表征非典型TCF3 FISH模式，如附加或减弱的TCF3信号所示。本文中，我们描述了使用下一代测序测定法（配对配对测序（MPseq））来表征典型和隐秘的TCF3 / PBX1融合物，并根据从我们实验室开发的TCF3 / PBX1 D-中获得的结果确定TCF3易位伙伴FISH探针组。对21例TCF3 / PBX1融合或无TCF3 / PBX1融合但通过我们的PBX1 / TCF3 D-FISH探针获得的TCF3信号减弱的小儿B-ALL / LBL进行MPseq。此外，对一名儿科B-ALL / LBL病例进行了MPseq检测，该病例具有明显的核型和异常的TCF3断裂探针结果。通过MPseq成功评估的22个标本中，有13例（59％）表现出TCF3 / PBX1融合，包括3例先前未描述的插入重排。其余9例（41％）包含各种TCF3伙伴，包括6例TCF3 / ZNF384，以及1例TCF3 / HLF，TCF3 / FLI1和TCF3 / TEF。我们的结果说明了MPseq能够以比传统细胞遗传学方法更高的精度和准确性来表征TCF3重排。包括三种情况，以前没有进行过描述的插入重排。其余9例（41％）包含各种TCF3伙伴，包括6例TCF3 / ZNF384，以及1例TCF3 / HLF，TCF3 / FLI1和TCF3 / TEF。我们的结果说明了MPseq能够以比传统细胞遗传学方法更高的精度和准确性来表征TCF3重排。包括三种情况，以前没有进行过描述的插入重排。其余9例（41％）包含各种TCF3伙伴，包括6例TCF3 / ZNF384，以及1例TCF3 / HLF，TCF3 / FLI1和TCF3 / TEF。我们的结果说明了MPseq能够以比传统细胞遗传学方法更高的精度和准确性来表征TCF3重排。

更新日期：2019-10-02

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