PDF(Pubmed)
Abstract：
NTRK-rearranged uterine sarcoma is a recently described entity that represents a subset of uterine sarcomas with distinct clinicopathological features. From a molecular point of view, this tumour is defined by NTRK gene rearrangement, resulting in overexpression or constitutive activation of Trk receptors. The presence of NTRK fusion is indicative of treatment response with a selective small-molecule inhibitor of the Trk kinases. Here, we report a case of an NTRK-rearranged sarcoma of the uterine cervix in a 43-year-old patient, measuring 80 mm in its largest dimension, with a novel NUMA1-NTRK1 fusion, not previously reported in NTRK-rearranged uterine sarcomas or other NTRK-rearranged tumours. The fusion, involving NUMA1 exon 14 (NM_006185.4) and NTRK1 exon 11 (NM_002529.4), was identified by next-generation sequencing (NGS) studies (FusionPlex Pan Solid Tumor v2 panel). Although the presence of NTRK fusion has been reported in a variety of neoplasms, a fusion involving NUMA1 (nuclear mitotic apparatus protein 1) and a tyrosine kinase partner has previously been reported in human neoplasms only in a handful of cases. The resulting fusion protein comprises the oligomerization domain of NUMA1, which is predicted to cause constant activation of the tyrosine kinase domain of NTRK1. The recognition and accurate diagnosis of these tumours are important due to the availability of potential targeted therapeutic options.
摘要：
NTRK重排子宫肉瘤是最近描述的实体，代表具有独特临床病理特征的子宫肉瘤子集。从分子的角度来看，这种肿瘤由NTRK基因重排定义，导致Trk受体的过表达或组成型激活。NTRK融合物的存在指示用Trk激酶的选择性小分子抑制剂的治疗反应。这里,我们报告了一个43岁的NTRK重排子宫颈肉瘤的病例，最大尺寸为80毫米，与一个新的NUMA1-NTRK1融合，以前未在NTRK重排的子宫肉瘤或其他NTRK重排的肿瘤中报告。融合，涉及NUMA1外显子14（NM_006185.4）和NTRK1外显子11（NM_002529.4），通过下一代测序(NGS)研究(FusionPlexPan实体瘤v2面板)鉴定。尽管NTRK融合的存在已被报道在多种肿瘤中，先前仅在少数病例中报道了涉及NUMA1（核有丝分裂器蛋白1）和酪氨酸激酶伴侣的融合。所得的融合蛋白包含NUMA1的寡聚化结构域,预测其引起NTRK1的酪氨酸激酶结构域的恒定活化。由于潜在的靶向治疗选择的可用性,这些肿瘤的识别和准确诊断是重要的。
