Detection of somatic genetic drivers is important for risk stratification and treatment selection in pediatric leukemias; however, newly recognized genetic markers may not be detected by routine karyotyping and fluorescence in situ hybridization (FISH). To identify the combination of assays that provides the highest detection rate for clinically significant molecular abnormalities, we tested 160 B- lymphoblastic leukemia (B-ALL) by karyotyping, FISH, chromosomal microarray analysis (CMA) and the custom next-generation sequencing (NGS) panel, OncoKids^Ⓡ. In addition, we tested 40 myeloid malignancies with karyotyping, chromosomal microarray analysis (CMA), and OncoKids^Ⓡ; 36/40 myeloid malignancies were also tested with FISH. In B-ALL, individual testing methods had the following diagnostic yields for the key genetic drivers: karyotype 34%; basic FISH panel 45%; FISH panel with IGH and CRLF2 probes 65%; CMA 48%; OncoKids^Ⓡ 39%. CMA and OncoKids^Ⓡ testing allowed detection of key genetic drivers in 42% of the samples that remained unknown upon testing by conventional methods. In myeloid malignancies, OncoKids^Ⓡ had the highest yield for detection of both primary and secondary DNA mutations and RNA fusions. Our data highlights the complementarity between CMA and NGS and conventional cytogenetics/FISH in pediatric leukemia diagnostics. Due to rapid turn-around-time, FISH may be useful as an initial screening method in B-ALL. Our data also suggests NGS testing with a comprehensive panel, despite a longer turnaround time, is a good alternative to karyotyping and FISH in pediatric AML due to its superior detection rate.

检测体细胞遗传驱动因素对于儿童白血病的风险分层和治疗选择很重要；然而，新识别的遗传标记可能无法通过常规核型分析和荧光原位杂交 (FISH) 检测到。为了确定对临床显着分子异常提供最高检出率的检测组合，我们通过核型分析、FISH、染色体微阵列分析 (CMA) 和定制的下一代测序 (NGS) 测试了 160 名 B 淋巴细胞白血病 (B-ALL) ) 面板，OncoKids ^Ⓡ。此外，我们测试了40个髓系恶性血液病与核型分析，染色体微阵列分析（CMA），和OncoKids ^Ⓡ; 还使用 FISH 测试了 36/40 髓系恶性肿瘤。在 B-ALL 中，个别检测方法对关键遗传驱动因素的诊断率如下：核型 34%；基本 FISH 面板 45%；带有 IGH 和 CRLF2 探针的 FISH 面板 65%；CMA 48%；OncoKids ^Ⓡ 39%。CMA 和 OncoKids ^Ⓡ测试允许在 42% 的样本中检测到关键的遗传驱动因素，而这些样本在通过传统方法测试时仍然未知。在髓系恶性肿瘤中，OncoKids ^Ⓡ在检测初级和次级 DNA 突变和 RNA 融合方面的产量最高。我们的数据突出了 CMA 和 NGS 与常规细胞遗传学/FISH 在儿童白血病诊断中的互补性。由于周转时间快，FISH 可用作 B-ALL 的初步筛查方法。我们的数据还表明，尽管周转时间较长，但使用综合面板进行 NGS 检测是一种很好的替代核型分析和 FISH 的儿科 AML，因为它具有较高的检出率。