Uterine MEIS1::NCOA2 Fusion Sarcoma With Lung Metastasis: A Case Report and Review of the Literature

Abstract

NCOA1/2 fusion sarcomas are a recently described novel entity arising in a variety of locations with a predilection for the genitourinary tract and gynecologic organs. Despite multiple locoregional recurrences, these tumors are thought to behave in a low-grade malignant manner. Here we report a uterine MEIS1::NCOA2 fusion sarcoma with lung metastasis. The patient was a 47-yr-old woman with a history of abnormal uterine bleeding who was found to have a myometrial mass confirmed by pathology to be uterine sarcoma. The tumor was predominantly composed of monotonous spindle cells with scant cytoplasm, crowded nuclei, and brisk mitotic activity, growing in a fascicular and streaming pattern. The morphologic and immunophenotypic features were nonspecific and a diagnosis of high-grade uterine sarcoma with a differential of leiomyosarcoma versus high-grade endometrial stromal sarcoma was rendered. At the 27-mo follow-up, the patient was found to have a lung metastasis consisting of a monotonous round cell sarcoma. A retrospective RNA-based and DNA-based next-generation sequencing of the primary uterine sarcoma revealed a MEIS1::NCOA2 gene fusion, a c.94G > C/p.D32H mutation in exon 3 of CTNNB1 gene, HMGA2, and CDK4 gene amplification, and an intermediate/marginal level of MDM2 gene amplification. Polymerase chain reaction-based molecular analysis further demonstrated that the MEIS1::NCOA2 gene fusion and CTNNB1 somatic mutation were also present in the lung metastasis. This case represents the first case of such gynecologic sarcoma with distant (lung) metastasis, and the second metastatic case among all reported MEIS1::NCOA1/2 fusion sarcomas, highlighting the malignant metastatic potential of this emerging entity. Our case also indicates that HMGA2/CDK4/ MDM2 region amplification and CTNNB1 somatic mutation might be recurrent genetic events in this rare sarcoma subtype.

Presentation_1.pptx

“…These genes were not only highly upregulated by VGLL1 at the mRNA level but were also identified in the ChIP-seq analysis, indicating that VGLL1-TF complexes can interact with them directly. Interestingly, several studies have shown these genes to have roles in cancer cell proliferation, invasion, angiogenesis, and EMT transition (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Taken together, our findings provide additional mechanistic evidence that VGLL1 plays an important role in modulating the expression of specific genes involved in driving tumor progression.…”

Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes

“…These genes were not only highly upregulated by VGLL1 at the mRNA level but were also identified in the ChIP-seq analysis, indicating that VGLL1-TF complexes can interact with them directly. Interestingly, several studies have shown these genes to have roles in cancer cell proliferation, invasion, angiogenesis, and EMT transition ( 26 – 38 ). Taken together, our findings provide additional mechanistic evidence that VGLL1 plays an important role in modulating the expression of specific genes involved in driving tumor progression.…”

ALX4::NCOA2 rearranged round and spindle cell sarcoma

“…1 Gene fusions involving NCOA2 with other fusion partners have been documented across various tumour types. These encompass acute myeloid leukaemia, 2 a small subset of colorectal carcinomas, 3 a single instance of myoepithelial carcinoma originating from the parotid gland, 4 an ependymoma-like tumour, 5 and a broadening array of distinct mesenchymal neoplasms, including mesenchymal chondrosarcoma, 6 soft-tissue angiofibroma, 7 PRRX:: NCOA1/2 rearranged fibroblastic neoplasm, 8 intraosseous spindle cell rhabdomyosarcoma, 9 congenital/infantile spindle cell rhabdomyosarcoma, 10 biphenotypic sinonasal sarcoma, 11 MEIS1::NCOA2/1 spindle cell sarcoma of the kidney, 12 uterine sarcoma with MEIS1:: NCOA2 fusion, 13 and uterine tumour resembling ovarian sex cord tumour. 14 Furthermore, singular cases of CRTC1::NCOA2 rearranged aggressive myxoid mesenchymal neoplasm involving the prostate, 15 two instances of MEF2D::NCOA2 rearranged smooth muscle tumours of the vulva, 16 as well as an NR1D1::NCOA2 rearranged soft-tissue tumour, 17 and an SRF::NCOA2 rearranged perivascular tumour of the philtrum, 18 have been reported.…”