Laboratory for Molecular Diagnostics, Department of Clinical Biology, Jessa Hospital, Hasselt, Belgium.
Department Jessa & Science, LCRC (-MHU), Hasselt, Belgium.
Virchows Arch. 2024 Aug;485(2):269-279. doi: 10.1007/s00428-023-03649-9. Epub 2023 Sep 21.
In addition to morphologic analysis, molecular diagnostic work up of Spitz tumours is often of great value for their accurate diagnosis/classification. Nowadays, next-generation sequencing (NGS) is the predominant screening method in molecular diagnostics. Up to 80% of these melanocytic neoplasms comprise gene fusions as genetic anomalies for which the driver codes for a protein harbouring a kinase domain. However, because of the variety of fusion partners the use of PCR-based targeted enrichment NGS methods is not recommended. We describe a series of four Spitz tumour samples in which distinct gene fusions were detected by hybridisation-based capture NGS (TPM3::ALK, LIMA1::ROS1, LRRFIP2::ROS1 and MYO5A::RET). Two of these fusions are not previously described. All 4 fusions were confirmed by reverse transcription-PCR. These findings demonstrate the need for molecular analysis that can detect unknown fusions in Spitz neoplasms for optimal diagnosis.
除形态分析外，Spitz 肿瘤的分子诊断分析对于其准确诊断/分类通常具有重要价值。目前，下一代测序（NGS）是分子诊断中的主要筛查方法。高达 80%的这些黑素细胞肿瘤包含基因融合作为遗传异常，其驱动基因编码具有激酶结构域的蛋白质。然而，由于融合伙伴的多样性，不建议使用基于 PCR 的靶向富集 NGS 方法。我们描述了一系列四个 Spitz 肿瘤样本，通过杂交捕获 NGS（TPM3::ALK、LIMA1::ROS1、LRRFIP2::ROS1 和 MYO5A::RET）检测到不同的基因融合。其中两个融合以前没有描述过。所有 4 个融合均通过逆转录-PCR 得到确认。这些发现表明需要进行分子分析，以在 Spitz 肿瘤中检测未知融合，从而实现最佳诊断。
