Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma

Sekine, Shigeki; Kiyono, Tohru; Ryo, Eijitsu; Ogawa, Reiko; Wakai, Susumu; Ichikawa, Hitoshi; Suzuki, Koyu; Arai, Satoru; Tsuta, Koji; Ishida, Mitsuaki; Sasajima, Yasushi; Goshima, Naoki; Yamazaki, Naoya; Mori, Taisuke

doi:10.1172/jci126185

Cited by 166 publications

(333 citation statements)

References 32 publications

(38 reference statements)

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“…Mechanistically, it is notable that all the YAP1 and WWTR1 fusions detected in poromas and porocarcinomas harbored the N‐terminal TEAD‐binding domain of YAP1 or WWTR1 fused to a C‐terminal MAML2‐ or NUTM1‐derived region that interacts with CBP and p300 transcriptional coactivators . The YAP1 and WWTR1 fusions were able to transactivate a TEAD reporter and demonstrated their transformational capacity by promoting anchorage‐independent growth in NIH3TC and dermal cells . Furthermore, YAP1‐NUTM1 fusions were enriched in porocarcinomas and poromas with primarily dermal localization, implying a link between specific fusions and clinicopathologic features.…”

Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

“…67 The YAP1 and WWTR1 fusions were able to transactivate a TEAD reporter and demonstrated their transformational capacity by promoting anchorage-independent growth in NIH3TC and dermal cells. 67 Evidence for ALL-associated NUTM1 fusions first emerged from a comprehensive genetic and transcriptomic study of MLL-and non-MLL-rearranged ALL in infants and children. 72 Two new fusions, BRD9-NUTM1, and apoptotic chromatin condensation inducer 1 (ACIN1)-NUTM1, were detected in non MLL-rearranged infants.…”

Section: Max Dimerization Protein (Mad)-nutm1 Tumorsmentioning

confidence: 99%

“…The repertoire of solid tumors harboring NUTM1 fusions was recently expanded with a report demonstrating their common occurrence in poromas and porocarcinomas . Poromas are benign sweat gland‐derived skin tumors.…”

Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

“…Like NUTM1, MAML2 interacts with p300 and this is crucial for CRTC1‐MAML2 transforming ability . Mechanistically, it is notable that all the YAP1 and WWTR1 fusions detected in poromas and porocarcinomas harbored the N‐terminal TEAD‐binding domain of YAP1 or WWTR1 fused to a C‐terminal MAML2‐ or NUTM1‐derived region that interacts with CBP and p300 transcriptional coactivators . The YAP1 and WWTR1 fusions were able to transactivate a TEAD reporter and demonstrated their transformational capacity by promoting anchorage‐independent growth in NIH3TC and dermal cells .…”

Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

“…A targeted sequencing panel against 114 cancer‐associated genes was used to analyse 23 poromas and 9 porocarcinomas . Unusually for NRNs a significant number of protein‐altering variants were detected, with poromas and porocarcinomas averaging one and three mutations per lesion respectively.…”

Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

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Emerging entities in NUTM1‐rearranged neoplasms

McEvoy

Fox

Prall

2020

Genes Chromosomes & Cancer

106

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Structural alterations of NUTM1 were originally thought to be restricted to poorly differentiated carcinomas with variable squamous differentiation originating in the midline organs of children and adolescents. Termed NUT carcinomas (NCs), they were defined by a t(15;19) chromosomal rearrangement that was found to result in a BRD4‐NUTM1 gene fusion. However, the use of DNA and RNA‐based next‐generation sequencing has recently revealed a multitude of new NUTM1 fusion partners in a diverse array of neoplasms including sarcoma‐like tumors, poromas, and acute lymphoblastic leukemias (ALLs) that we propose to call NUTM1‐rearranged neoplasms (NRNs). Intriguingly, the nosology of NRNs often correlates with the functional classification of the fusion partner, suggesting different oncogenic mechanisms within each NRN division. Indeed, whereas NCs are characterized by their aggressiveness and intransigence to standard therapeutic measures, the more positive clinical outcomes seen in some sarcoma and ALL NRNs may reflect these mechanistic differences. Here we provide a broad overview of the molecular, nosological, and clinical features in these newly discovered neoplastic entities. We describe how aberrant expression of NUTM1 due to fusion with an N‐terminal DNA/chromatin‐binding protein can generate a potentially powerful chromatin modifier that can give rise to oncogenic transformation in numerous cellular contexts. We also conclude that classification, clinical behavior, and therapeutic options may be best defined by the NUTM1 fusion partner rather than by tumor morphology or immunohistochemical profile.

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Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

Section: Max Dimerization Protein (Mad)-nutm1 Tumorsmentioning

confidence: 99%

Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

Section: Other Nutm1‐associated Solid Tumorsmentioning

confidence: 99%

See 3 more Smart Citations

Emerging entities in NUTM1‐rearranged neoplasms

McEvoy

Fox

Prall

2020

Genes Chromosomes & Cancer

106

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Tumours of Skin Appendages

Calonje,

Marušić

2024

Rook's Textbook of Dermatology

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The clinical presentation of skin appendage tumours for the most part is not as specific and diverse as the histological features of this extremely heterogeneous tumour group. Differential diagnosis of certain appendageal tumours can be extremely subtle, yet greatly influence final treatment outcome. Occasional association of certain entities with inherited tumour syndrome s can be extremely important in terms of hereditary cancer screening. This chapter aims to provide the most important clinical, histological and genetic features for selected, most important cutaneous appendage tumours.

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A case of metastatic NUT carcinoma with prolonged response on gemcitabine and nab‐paclitaxel

Patel

Singer

Shen

et al. 2021

Clinical Case Reports

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Background NUT carcinoma is an aggressive malignancy characterized by translocations in the NUTM1 gene. There are currently no consensus treatment recommendations for NUT carcinomas. Methods Here, we describe the case of a previously healthy male diagnosed with NUT carcinoma after presenting with sinus pressure, found to have a sinonasal mass and distant metastatic disease in the lungs. While pathologic evaluation and immunohistochemistry were consistent with NUT carcinoma, initial genomic profiling did not demonstrate a NUTM1 translocation. Results Whole transcriptomic RNA sequencing of the tumor revealed a YAP1 ‐ NUTM1 fusion. Based on an in vitro drug sensitivity screen, the patient was treated with gemcitabine and nab‐paclitaxel, achieving a partial response that persisted for 9 months. Conclusions Unbiased transcriptomic sequencing may identify previously uncharacterized NUTM1 fusion partners. Gemcitabine and nab‐paclitaxel is a well‐tolerated combination chemotherapy regimen and could offer a novel treatment approach for NUT carcinoma.

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Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma

Cited by 166 publications

References 32 publications

Emerging entities in NUTM1‐rearranged neoplasms

Emerging entities in NUTM1‐rearranged neoplasms

Tumours of Skin Appendages

A case of metastatic NUT carcinoma with prolonged response on gemcitabine and nab‐paclitaxel

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