Stadt Udo Zur, Escherich Gabriele, Indenbirken Daniela, Alawi Malik, Adao Manuela, Horstmann Martin A
Center for Diagnostics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Pediatr Blood Cancer. 2016 Jul;63(7):1283-6. doi: 10.1002/pbc.25975. Epub 2016 Mar 23.
Comprehensive next-generation sequencing (NGS) applications have recently identified various recurrent kinase and cytokine receptor rearrangements in Ph-like B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) amenable to tyrosin kinase inhibitor treatment. For rapid diagnostics of kinase pathway aberrations in minimal residual disease (MRD) high-risk BCP-ALL, we developed a PCR-independent NGS custom enrichment capture panel targeting recurrent genomic alterations, which allows for the identification of unknown 5' fusion partner genes and precise mapping of variable genomic breakpoints. Using a standardized bioinformatics algorithm, we identified kinase and cytokine receptor rearrangements in the majority of ALL patients with high burden of postinduction MRD and enrichment of IKZF1 mutation or deletion (IKZF1(del) ).
全面的下一代测序（NGS）应用最近在费城样B细胞前体（BCP）急性淋巴细胞白血病（ALL）中发现了各种复发性激酶和细胞因子受体重排，这些重排适合酪氨酸激酶抑制剂治疗。为了快速诊断微小残留病（MRD）高危BCP-ALL中的激酶通路异常，我们开发了一种独立于PCR的NGS定制富集捕获面板，靶向复发性基因组改变，该面板可识别未知的5'融合伙伴基因并精确绘制可变基因组断点。使用标准化的生物信息学算法，我们在大多数诱导后MRD负担高且IKZF1突变或缺失（IKZF1（del））富集的ALL患者中鉴定出激酶和细胞因子受体重排。
