Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NUT carcinoma (NC) shows very aggressive clinical behavior, occurs predominantly in the thorax and head and neck region of children and adults, and is defined by the presence of NUT (aka NUTM1) rearrangement, mostly BRD4-NUTM1 fusion resulting from t(15;19)(q13; p13.1). So-called "NUT variants" harbor alternate fusions between NUTM1 and BRD3, NSD3, ZNF532, or unknown partners. Rare cases of pediatric tumors with CIC-NUTM1 fusion were recently reported in somatic soft tissue, brain, and kidney. However, such cases have not been identified in adult patients and the presence of a fusion between CIC, characteristic of CIC-rearranged sarcoma, and NUTM1-a defining feature of NC-poses a diagnostic challenge. We herein report a case of malignant epithelioid neoplasm with myoepithelial features harboring CIC-NUTM1 fusion arising in soft tissue of the head in a 60-year-old man. Immunohistochemistry revealed strong expression of NUT, but only weak ETV4 staining and negativity for keratins, EMA, p40, CD99, and WT1. SMARCB1 expression was retained. Fluorescence in situ hybridization and targeted next-generation sequencing identified a CIC-NUTM1 fusion resulting from t(15;19)(q14;q13.2). In light of morphologic features that overlap with those of NC from typical anatomical sites we have seen previously, the tumor was best classified as falling within the NC spectrum rather than CIC-associated sarcoma. This case highlights the emerging diagnostic challenges generated by newly detected gene fusions of unknown clinical and biologic significance. Careful integration of cytogenetic, molecular, and immunohistochemical findings with morphologic appearances in the diagnostic workup of undifferentiated neoplasms is essential.
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PMID:CIC-NUTM1 fusion: A case which expands the spectrum of NUT-rearranged epithelioid malignancies. 2970 Aug 87

NUTM1 gene rearrangement is the genetic hallmark of NUT carcinoma, an aggressive tumor that most commonly affects the thoracic and head and neck regions and often exhibits squamous differentiation. The most common fusion partner gene is BRD4, followed by BRD3 and NSD3. Recently, NUTM1 gene rearrangement has been identified in rare tumors from soft tissues, intracranial locations, and other visceral organs. These tumors often show high grade malignant epithelioid to round cell histomorphology and lack evidence of squamous and/or epithelial differentiation. Therefore, their relationship with classic NUT carcinoma is still uncertain. Here, we present a primary mandible bone tumor of a 21-year-old female exhibiting monotonous epithelioid and rhabdoid cytomorphology, vesicular chromatin, and prominent nucleoli. The initial immunohistochemical workup was non-specific, showing only CD34 positivity while being negative for cytokeratin (AE1/AE3), EMA, p63, etc. INI-1 expression was retained. RNA sequencing was performed and identified a rare ZNF532-NUTM1 gene fusion, which had only been reported in a single case of pulmonary NUT carcinoma. The fusion was confirmed by FISH for NUTM1 gene rearrangement and supported by diffuse and strong NUT immunoreactivity. MYC mRNA up-regulation and immunoreactivity, a common finding in NUT carcinoma, was also observed in this tumor, suggesting a possible common pathogenetic mechanism and potential treatment target. The patient presented with a non-metastatic disease status and received hemimandibulectomy, selective neck dissection (level Ib), and post-operative radiation therapy. She remained disease free 3.6 years after the initial diagnosis.
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PMID:Primary malignant epithelioid and rhabdoid tumor of bone harboring ZNF532-NUTM1 fusion: the expanding NUT cancer family. 3133 71