Vanhevel Justine, Rack Katrina, Ameye Geneviève, Mokrani Hayat, De Bie Jolien, Michaux Lucienne, Dewaele Barbara
Laboratory for the Cytogenetic and Molecular Diagnosis of Hematological Malignancies, Centre for Human Genetics, University Hospitals, Leuven, Belgium.
Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint-Antoine, Paris, France.
J Cell Mol Med. 2025 Jun;29(12):e70640. doi: 10.1111/jcmm.70640.
Myeloid/Lymphoid Neoplasms with eosinophilia and involvement of Tyrosine Kinase gene fusions (MLN-TK) is a WHO disease category including a diverse group of malignancies characterised by recurrent genomic rearrangements of tyrosine kinase (TK) genes such as PDGFRA, PDGFRB, FGFR1, JAK2, ETV6 and FLT3. Identification of these TK rearrangements is important for the accurate diagnosis of MLN-TK and allows targeted therapy with TK inhibitors. In this study, we validated the use of optical genome mapping (OGM) retrospectively by analysing 11 samples from 10 cases with suspected or known TK rearrangements, previously analysed by current standard of care (SOC) methodologies, i.e., chromosome banding analysis (CBA), FISH and/or PCR-based techniques. In six abnormal cases, OGM was able to detect the rearrangements previously determined by SOC methods. Furthermore, OGM identified the fusion partner in the JAK2- and PDGFRB-rearranged cases and elucidated the mechanism underlying the BCR::FGFR1 and ETV6::SYK rearrangement. In two cases with a normal karyotype, OGM detected two cryptic FIP1L1::PDGFRA and TNIP1::PDGFRB rearrangements. In the two remaining cases, no abnormalities were detected either by OGM or SOC methods. We demonstrate that OGM is a valid technique for the diagnostic workflow of MLN-TK, able to detect TK rearrangements and to identify unknown TK fusion partners.
伴有嗜酸性粒细胞增多及酪氨酸激酶基因融合的髓系/淋系肿瘤（MLN-TK）是世界卫生组织（WHO）的一个疾病类别，包括一组多样的恶性肿瘤，其特征为酪氨酸激酶（TK）基因如PDGFRA、PDGFRB、FGFR1、JAK2、ETV6和FLT3发生反复的基因组重排。识别这些TK重排对于MLN-TK的准确诊断很重要，并且能使TK抑制剂进行靶向治疗。在本研究中，我们通过分析来自10例疑似或已知TK重排病例的11份样本，对光学基因组图谱（OGM）的使用进行了回顾性验证，这些样本之前已通过当前的标准治疗（SOC）方法进行分析，即染色体显带分析（CBA）、荧光原位杂交（FISH）和/或基于聚合酶链反应（PCR）的技术。在6例异常病例中，OGM能够检测到SOC方法先前确定的重排。此外，OGM在JAK2和PDGFRB重排病例中识别出融合伴侣，并阐明了BCR::FGFR1和ETV6::SYK重排的潜在机制。在2例核型正常的病例中，OGM检测到2种隐匿性FIP1L1::PDGFRA和TNIP1::PDGFRB重排。在其余2例病例中，OGM和SOC方法均未检测到异常。我们证明OGM是MLN-TK诊断流程中的一种有效技术，能够检测TK重排并识别未知的TK融合伴侣。
