<i>NUT</i> carcinoma in children and adults: A multicenter retrospective study

Lemelle, Lauriane; Pierron, Gaëlle; Fréneaux, Paul; Huybrechts, Sophie; Spiegel, A.; Plantaz, Dominique; Juliéron, M.; Dumoucel, Sophie; Italiano, Antoîne; Millot, Frédéric; Tourneau, Christophe Le; Leverger, Guy; Chastagner, Pascal; Carton, Matthieu; Orbach, Daniel

doi:10.1002/pbc.26693

Cited by 74 publications

(117 citation statements)

References 43 publications

Supporting

Mentioning

109

Contrasting

Order By: Relevance

“…Similarly, our six patients who underwent upfront surgery survived significantly longer than the others, and two of them with stage IV disease (NC2 and 3) survived for approximately 2 years. Although long‐term remission in response to chemoradiotherapy without surgery was reported in two patients previously , the benefit of chemotherapy or radiotherapy without surgery was unclear . In our patients, the long‐term survivor, NC3 underwent aggressive gross total resection, including metastasectomy plus chemoradiotherapy, which suggests the important role of local modalities in the treatment of advanced NUT carcinoma.…”

Section: Discussionmentioning

confidence: 64%

“…The median age of patients was 48.0 years, which was older than that reported previously (Table ) . Because of its rarity and undifferentiated histology, NUT carcinoma is often misdiagnosed in 61.5% of cases in our series and 50%‐66% of other cases as other tumors, including undifferentiated and poorly differentiated carcinoma, sinonasal undifferentiated carcinoma, and Ewing sarcoma/primary neuroectodermal tumor . In our archived head and/or neck carcinoma data set, 40% of tumors initially diagnosed as sinonasal undifferentiated carcinoma were subsequently diagnosed as NUT carcinoma .…”

Section: Discussionmentioning

confidence: 67%

“…Although NUT carcinoma has a dismal outcome (median OS, 4.7‐9.7 months), upfront and intensive local approaches, such as gross total resection and radiotherapy, may provide survival benefits (Table ) . Similarly, our six patients who underwent upfront surgery survived significantly longer than the others, and two of them with stage IV disease (NC2 and 3) survived for approximately 2 years.…”

Section: Discussionmentioning

confidence: 82%

See 2 more Smart Citations

Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study

et al. 2019

View full text Add to dashboard Cite

Background NUT carcinoma is a rare aggressive disease caused by BRD4/3‐NUT fusion, and C‐MYC upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC‐targeting agents against patient‐derived NUT carcinoma cell lines. Materials and Methods Thirteen patients with NUT carcinoma were evaluated for p53, C‐MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD‐L1) by immunohistochemistry. The half maximal inhibitory concentration (IC50) values of NUT carcinoma cell lines (SNU‐2972‐1, SNU‐3178S, HCC2429, and Ty‐82) were determined using MYC‐targeting agents, including bromodomain and extraterminal (BET) inhibitors (I‐BET, OTX‐015, AZD5153) and histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, panobinostat, CUDC‐907). Results Primary tumor sites included head and neck (n = 9) and lung (n = 4). The patient age ranged from 8 to 73 years with the male/female ratio of 1.2:1. Nine patients died at 3–23.6 months (median, 10.6) after diagnosis. Eight patients had been misdiagnosed initially with other diseases. One patient with metastatic NUT carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a long‐term survivor (>27 months). Although expressions of C‐MYC (8/12, 73%) and p53 (12/12, 100%) were commonly observed, EGFR, HER2, and PD‐L1 expressions were observed in 2 of 7 (29%), 2 of 8 (25%), and 1 of 12 (8.3%) patients, respectively. BET and HDAC inhibitors showed variable but limited in vitro efficacy. However, a dual HDAC/PI3K inhibitor, CUDC‐907, was most potent against NUT carcinoma cells, with an IC50 of 5.5–9.0 pmol/L. Consistent with these findings, kinome short interfering RNA screening showed a positive hit for PI3KCA in NUT carcinoma cells. Panobinostat (IC50, 0.4–1.3 nmol/L) and a bivalent BET inhibitor, AZD5153 (IC50, 3.7–8.2 nmol/L), also showed remarkable efficacies. Conclusion East Asian patients with NUT carcinoma showed dismal survival outcomes like Western patients, and CUDC‐907 might be promising in NUT carcinoma treatment. Implications for Practice NUT carcinoma (NC) is a disease caused by BRD‐NUT fusion leading to C‐MYC upregulation. NC is often misdiagnosed and very aggressive, requiring development of effective therapeutic strategy. This article presents the clinicopathological features of the largest series of NCs in East Asians and preclinical sensitivities to MYC‐targeting agents in NC cell lines. Patients with NC had grave outcomes and poor response to treatment. Among MYC‐targeting agents, including BET and HDAC inhibitors, CUDC‐907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC‐907 might be promising in NC treatment.

show abstract

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 82%

See 1 more Smart Citation

Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study

et al. 2019

View full text Add to dashboard Cite

show abstract

“…NUTM1 (8 exons) encodes for a protein physiologically restricted to the testes and ovary but whose function is unknown . Its rearrangement is the hallmark of NUT midline carcinoma, an aggressive subtype of squamous cell carcinoma . In this pathology, almost all the NUTM1 sequence (with the exception of the first exon) is conserved in the fusion transcript, which has been shown to result in aberrant chromatin regulation and consistent hyperexpression of MYC .…”

Section: Discussionmentioning

confidence: 99%

Cryptic recurrent ACIN1‐NUTM1 fusions in non‐KMT2A‐rearranged infant acute lymphoblastic leukemia

Pincez

Landry

Roussy

et al. 2019

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Infant acute lymphoblastic leukemias (ALL) are rare hematological malignancies occurring in children younger than 1 year of age, most frequently associated with KMT2A rearrangements (KMT2A‐r). The smaller subset without KMT2A‐r, which represents 20% of infant ALL cases, is poorly characterized. Here we report two cases of chemotherapy‐sensitive non‐KMT2A‐r infant ALL. Transcriptome analyses revealed identical ACIN1‐NUTM1 gene fusions in both cases, derived from cryptic chromosomal rearrangements undetected by standard cytogenetic approaches. Two isoforms of the gene fusion, joining exons 3 or 4 of ACIN1 to exon 3 of NUTM1, were identified. Both fusion transcripts contained the functional DNA‐binding SAP (SAF‐A/B, Acinus, and PIAS) domain of ACIN1 and most of NUTM1. The detection of the ACIN1‐NUTM1 fusion by RT‐PCR allowed the molecular monitoring of minimal residual disease in a clinical setting. Based on publicly available genomic datasets and literature review, we predict that NUTM1 gene fusions are recurrent events in infant ALL. As such, we propose two clinically relevant assays to screen for NUTM1 rearrangements in bone marrow cells, independent of the fusion partner: NUMT1 immunohistochemistry and NUTM1 RNA expression. In sum, our study identifies ACIN1‐NUTM1 as a recurrent and possibly cryptic fusion in non‐KMT2A‐r infant ALL, provides clinical tools to screen for NUTM1‐rearranged leukemia and contributes to the refinement of this new subgroup.

show abstract

“…For clinical outcome, the median survival is only 5 months and the 2‐year OS is no more than 10% . Interestingly, all of the three long‐time survivors (＞10 years) of patients with NMC were also those treated with a combination of radiotherapy/chemotherapy …”

Section: Discussionmentioning

confidence: 99%

Successful treatment of a case with NUT midline carcinoma in the larynx and review of the literature

Zhang¹,

Liu²,

Zhang

et al. 2019

Clinical Case Reports

View full text Add to dashboard Cite

show abstract

NUT carcinoma in children and adults: A multicenter retrospective study

Cited by 74 publications

References 43 publications

Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study

Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study

Cryptic recurrent ACIN1‐NUTM1 fusions in non‐KMT2A‐rearranged infant acute lymphoblastic leukemia

Successful treatment of a case with NUT midline carcinoma in the larynx and review of the literature

Contact Info

Product

Resources

About