NTRK-rearranged spindle cell sarcoma of the uterine cervix with a novel NUMA1::NTRK1 fusion

AbstractNTRK-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 byNTRK gene rearrangement, resulting in overexpression or constitutive activation of Trk receptors. The presence ofNTRK fusion is indicative of treatment response with a selective small-molecule inhibitor of the Trk kinases. Here, we report a case of anNTRK-rearranged sarcoma of the uterine cervix in a 43-year-old patient, measuring 80  mm in its largest dimension, with a novelNUMA1-NTRK1 fusion, not previously reported inNTRK-rearranged uterine sarcomas or otherNTRK-rearranged tumours. The fusion, involvingNUMA1 exon 14 (NM_006185.4) andNTRK1 exon 11 (NM_002529.4), was identified by next-generation sequencing (NGS) studies (FusionPlex Pan Solid Tumor v2 panel). Although the presence ofNTRK fusion has been reported in a variety of neoplasms, a fusion involvingNUMA1 (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.
Source: Virchows Archiv - Category: Pathology Source Type: research