NUTM1 (NUT Midline Carcinoma Family Member 1)

Accordingly, molecular analysis of the cases revealed the presence of an in-frame YAP1::MAML2 fusion transcript. To conclude, our cases confirmed that YAP1 fusions are the oncogenic drivers of a subset of adnexal tumors that may harbor poroid, follicular but also sebaceous differentiation.

Given the limited treatment options for NUT carcinoma, a combination of ICIs with platinum-based chemotherapy may represent a potential first-line treatment option. However, their efficacy remains limited.

This article examines cutaneous neoplasms with NUTM1 gene fusions, focusing on poroma, porocarcinoma, and primary cutaneous NUT carcinoma. Diagnostic challenges include differentiating primary cutaneous NUT carcinoma from extracutaneous NUT carcinoma and porocarcinoma, for which immunohistochemistry (NUT, SOX10, YAP1) and molecular testing are essential.

PRAME is highly and frequently expressed in NUT carcinoma, and the most common oncoprotein causing NUT carcinoma, BRD4::NUTM1, contributes to these high PRAME levels. PRAME epitopes presented by HLA class I are a previously unrecognized therapeutic vulnerability for NUT carcinoma that warrants clinical trials testing PRAME-targeted immunotherapies in this neglected patient population.

He was treated with nine cycles of VDC-IE(vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) chemotherapy given at 3-week intervals, complicated by transient iron deficiency anaemia, followed by surgical excision with neck dissection and fibular flap reconstruction. Maintenance therapy with the histone deacetylase inhibitor vorinostat was initiated. This case highlights the importance of early recognition, multimodal therapy and emerging targeted treatment in improving outcomes for NUT carcinoma.

Primary uterine NUT carcinoma may be misdiagnosed as other undifferentiated uterine tumors due to its rarity and histological overlap. Given the diagnostic challenges, NUT IHC staining and molecular testing for NUTM1 rearrangement should be considered in undifferentiated uterine tumors with ambiguous histopathological features.

Our findings indicate that the CIC fusion binding partner may alter overall fusion oncoprotein activity. Implications: These first-generation synthetic tools illuminate partner gene-specific mechanistic biology while providing an unprecedented resource to study CIC-family fusions beyond CIC::DUX4 and allow for the dissection of this rare subgroup of cancers.

P1/2, N=36, Recruiting, National Cancer Institute (NCI) | Phase classification: P1 --> P1/2

MDA-NUT87 and MDA-NUT88 are the first stable human sinonasal NUT carcinoma cell lines established from the primary tumor site. They preserve the hallmark genetic and phenotypic characteristics of NUT carcinoma and show sensitivity to BET inhibition. These models represent valuable tools for mechanistic studies and high-throughput drug screening in sinonasal NUT carcinoma.

This vulnerability is mechanistically linked to the leukemia's dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, revealing specific vulnerabilities that rationalize their favorable clinical outcomes and suggest opportunities for modified therapeutic strategies.

P1, N=36, Recruiting, National Cancer Institute (NCI) | Phase classification: P1/2 --> P1 | N=55 --> 36

Molecular testing identified a BRD3-NUTM1 fusion, confirming the diagnosis of NUT adnexal carcinoma. The patient remains disease-free at 1-year follow-up without further therapy.