Traditional cytogenetic testing methodologies, including conventional chromosome analysis and fluorescence in situ hybridization (FISH), are invaluable for the detection or recurrent genetic abnormalities in various hematologic malignancies. However, technological advances, including a novel next-generation sequencing technique termed mate-pair sequencing (MPseq), continue to revolutionize the field of cytogenetics by enabling the characterization of structural variants at a significantly higher resolution compared to traditional methodologies. To illustrate the power of MPseq, we present a 27-year-old male diagnosed with chronic myeloid leukemia in myeloid blast crisis with multiple chromosomal abnormalities observed in all 20 metaphases from a peripheral blood specimen, including t(9;22)(q34;q11.2) and t(4;11)(q12;p15). Suspicious of a novel NUP98/PDGFRA fusion [t(4;11)(q12;p15)], break-apart FISH probe sets for the PDGFRA (4q12) and NUP98 (11p15.4) gene regions were performed and were both positive in approximately 86% of 200 interphase nuclei. However, subsequent MPseq testing revealed breakpoints located within the NUP98 gene and within an intergenic region (4q12) located between the CHIC2 and PDGFRA genes, indicating this 4;11 translocation does not result in the predicted NUP98/PDGFRA gene fusion as inferred from FISH and conventional chromosome results. This case demonstrates the clinical utility of MPseq, particularly for characterizing novel gene fusion events which may ultimately identify a false-positive FISH result.

传统的细胞遗传学检测方法，包括常规的染色体分析和原位荧光杂交（FISH）对于各种血液系统恶性肿瘤的检测或复发性遗传异常具有不可估量的价值。但是，包括称为配对配对测序（MPseq）的新型下一代测序技术在内的技术进步，通过使结构变体的表征能力比传统方法学高得多，继续在细胞遗传学领域掀起一场革命。为了说明MPseq的功能，我们介绍了一位27岁的男性，它被诊断为患有髓样细胞爆炸危机的慢性粒细胞白血病，在外周血标本的所有20个中期中均观察到多种染色体异常，包括t（9; 22）（q34; q11.2）和t（4; 11）（q12; p15）。可疑的新型NUP98 / PDGFRA融合体[t（4; 11）（q12; p15）]，可断裂的FISH探针组进行了PDGFRA（4q12）和NUP98（11p15.4）基因区域，它们在200个中间相核中约86％均为阳性。然而，随后的MPseq测试揭示了位于NUP98基因内以及位于CHIC2和PDGFRA基因之间的基因间区域（4q12）内的断点，表明这种4; 11易位并不能导致从FISH和HIF推断的NUP98 / PDGFRA基因融合预测常规染色体结果。该案例证明了MPseq的临床实用性，特别是在表征新的基因融合事件方面，这些事件可能最终鉴定出假阳性的FISH结果。