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.
