Fei Fei, Telatar Milhan, Tomasian Vanina, Chang Lisa, Gust Mariel, Yew Hooi, Dyer Tamerisa, Danilova Olga, Arias-Stella Javier, Pillai Raju, Aldoss Ibrahim, Stewart F Marc, Becker Pamela S, Pullarkat Vinod, Marcucci Guido, Afkhami Michelle
Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Int J Mol Sci. 2025 Jan 7;26(2):435. doi: 10.3390/ijms26020435.
Recurrent fusions drive the pathogenesis of many hematological malignancies. Compared to routine cytogenetic/fluorescence in situ hybridization (FISH) studies, the RNA-based next-generation sequencing (NGS) fusion assay enables the identification of both known and novel fusions. In many cases, these recurrent fusions are crucial for diagnosis and are associated with prognosis, relapse prediction, and therapeutic options. The aim of this study is to investigate the application of the RNA-based NGS fusion assay in hematological malignancies. Our study included 3101 cases with available fusion results, and a fusion event was identified in 17.6% of cases. The discordant rate between the RNA-based NGS fusion assay and cytogenetic/FISH studies was 36.3%. Further analysis of discordant cases indicated that, compared to cytogenetic/FISH studies, the RNA-based NGS fusion assay significantly improved the identification of cryptic fusion genes, such as , , and fusions involving different partners. Additionally, our study identified 24 novel fusions and 16 cases with the simultaneous presence of two fusions. These additional findings from the RNA-based NGS fusion assay resulted in improved risk stratification, disease targeting and monitoring. In conclusion, our study demonstrates the feasibility and utility of an RNA-based NGS fusion assay for patients with hematological malignancies, suggesting that it may be essential for the routine clinical workup of these patients.
复发性融合驱动许多血液系统恶性肿瘤的发病机制。与常规细胞遗传学/荧光原位杂交（FISH）研究相比，基于RNA的下一代测序（NGS）融合检测能够识别已知和新型融合。在许多情况下，这些复发性融合对诊断至关重要，并与预后、复发预测和治疗选择相关。本研究的目的是探讨基于RNA的NGS融合检测在血液系统恶性肿瘤中的应用。我们的研究纳入了3101例有可用融合结果的病例，17.6%的病例中发现了融合事件。基于RNA的NGS融合检测与细胞遗传学/FISH研究之间的不一致率为36.3%。对不一致病例的进一步分析表明，与细胞遗传学/FISH研究相比，基于RNA的NGS融合检测显著提高了对隐匿性融合基因的识别，如涉及不同伙伴的 、 和 融合。此外，我们的研究发现了24种新型融合以及16例同时存在两种融合的病例。基于RNA的NGS融合检测的这些额外发现改善了风险分层、疾病靶向和监测。总之，我们的研究证明了基于RNA的NGS融合检测对血液系统恶性肿瘤患者的可行性和实用性，表明它可能对这些患者的常规临床检查至关重要。
