Challenges and Opportunities in NUT Carcinoma Research

Hakun, Maxwell; Gu, Bin

doi:10.3390/genes12020235

“…Although the oncogenic impact of the ZNF532:: NUTM1 fusion in CNS tumors has not been studied, functional studies of other cancers have shown that NUTM1 fusion positive cells demonstrate lack of differentiation of epithelial cells and nuclear localization of the NUT protein, suggesting that NUTM1 fusions contribute to tumor development by associating with nuclear chromatin and interfering with cell differentiation [34,35]. Consistent with this finding, nearly all of our patient's tumor cells displayed homogeneous nuclear expression when using the monoclonal NUT antibody, confirming nuclear localization of the NUT protein in this tumor (NeoGenomics; Figure 1K).…”

Section: Discussionmentioning

confidence: 99%

Optical genome mapping identifies a novel pediatric embryonal tumor with a ZNF532::NUTM1 fusion

Bornhorst

¹

,

Eze

²

,

Bhattacharya

³

et al. 2023

The Journal of Pathology

4

0

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The molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have led to the introduction of novel treatment options for patients with specific tumor alterations. Therefore, an accurate histologic and molecular diagnosis is critical for optimized management of all pediatric patients with brain tumors, including central nervous system embryonal tumors. We present a case where optical genome mapping identified a ZNF532::NUTM1 fusion in a patient with a unique tumor best characterized histologically as a central nervous system embryonal tumor with rhabdoid features. Additional analyses including immunohistochemistry for NUT protein, methylation array, whole genome, and RNA‐sequencing was done to confirm the presence of the fusion in the tumor. This is the first description of a pediatric patient with a ZNF532::NUTM1 fusion, yet the histology of this tumor is similar to that of adult cancers with ZNF::NUTM1 fusions reported in the literature. Although rare, the distinct pathology and underlying molecular characteristics of the ZNF532::NUTM1 tumor separates this from other embryonal tumors. Therefore, screening for this or similar NUTM1 rearrangements should be considered for all patients with unclassified central nervous system tumors with rhabdoid features to ensure accurate diagnosis. Ultimately, with additional cases, we may be able to better inform therapeutic management for these patients. © 2023 The Pathological Society of Great Britain and Ireland.

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“…Although the oncogenic impact of the ZNF532-NUTM1 fusion in CNS tumors has not been studied, functional studies of other cancers have shown that NUTMI- fusion positive cells demonstrate lack of differentiation of epithelial cells and nuclear localization of the NUT protein, suggesting that NUTM1- fusions contributed to tumor development by associating with nuclear chromatin and interfering with cell differentiation [22,23]. Consistent with this finding, nearly all of our patient’s tumor cells displayed homogenous nuclear expression of the monoclonal NUT antibody confirming nuclear localization of the NUT protein in this tumor (NeoGenomics; Figure 1I).…”

Section: Discussionmentioning

confidence: 99%

Optical Genome Mapping Identifies a Novel Pediatric Embryonal Tumor Subtype with a ZNF532-NUTM1 Fusion

Bornhorst

¹

,

Eze

²

,

Bhattacharya

³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

Molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have introduced novel treatment options for patients with specific tumor alterations. Therefore, an accurate histologic and molecular diagnosis is critical for optimized management of all pediatric patients with brain tumors, including central nervous system embryonal tumors. We present a case where optical genome mapping identified a ZNF532-NUTM1 fusion in a patient with a unique tumor best characterized histologically as a central nervous system embryonal tumor with rhabdoid features. Additional analyses including immunohistochemistry for NUT protein, methylation array, whole genome, and RNA-sequencing was done to confirm the presence of the fusion in the tumor. This is the first description of a pediatric patient with a ZNF532-NUTM1 fusion, yet the histology of this tumor is similar to that of adult cancers with ZNF-NUTM1 fusions and other NUTM1-fusion positive brain tumors reported in literature. Although rare, the distinct pathology and underlying molecular characteristics of these tumors separate them from other embryonal tumors. Therefore, the NUTM-rearrangement appears to define a novel subgroup of pediatric central nervous system embryonal tumors with rhabdoid/epithelioid features that may have a unique response to treatment. Screening for a NUTM1-rearrangement should be considered for all patients with unclassified central nervous system tumors with rhabdoid features to ensure accurate diagnosis so this can ultimately inform therapeutic management for these patients.

show abstract

“…Although the oncogenic impact of the ZNF532-NUTM1 fusion in CNS tumors has not been studied, functional studies of other cancers have shown that NUTMI-fusion positive cells demonstrate lack of differentiation of epithelial cells and nuclear localization of the NUT protein, suggesting that NUTM1fusions contributed to tumor development by associating with nuclear chromatin and interfering with cell differentiation 31,32 . Consistent with this nding, nearly all of our patient's tumor cells displayed homogenous nuclear expression of the monoclonal NUT antibody con rming nuclear localization of the NUT protein in this tumor (NeoGenomics; Fig.…”

Section: Discussionmentioning

confidence: 99%

Optical Genome Mapping Identifies a Novel Pediatric Embryonal Tumor Subtype with a ZNF532-NUTM1 Fusion

Bornhorst

¹

,

Eze

²

,

Bhattacharya

³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

Molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have introduced novel treatment options for patients with specific tumor alterations. Therefore, an accurate histologic and molecular diagnosis is critical for optimized management of all pediatric patients with brain tumors, including central nervous system embryonal tumors. We present a case where optical genome mapping identified a ZNF532-NUTM1 fusion in a patient with a unique tumor best characterized histologically as a central nervous system embryonal tumor with rhabdoid features. Additional analyses including immunohistochemistry for NUT protein, methylation array, whole genome, and RNA-sequencing was done to confirm the presence of the fusion in the tumor. This is the first description of a pediatric patient with a ZNF532-NUTM1 fusion, yet the histology of this tumor is similar to that of adult cancers with ZNF-NUTM1 fusions and other NUTM1-fusion positive brain tumors reported in literature. Although rare, the distinct pathology and underlying molecular characteristics of these tumors separate them from other embryonal tumors. Therefore, the NUTM-rearrangement appears to define a novel subgroup of pediatric central nervous system embryonal tumors with rhabdoid/epithelioid features that may have a unique response to treatment. Screening for a NUTM1-rearrangement should be considered for all patients with unclassified central nervous system tumors with rhabdoid features to ensure accurate diagnosis so this can ultimately inform therapeutic management for these patients.

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Challenges and Opportunities in NUT Carcinoma Research

Cited by 11 publications

References 73 publications

Optical genome mapping identifies a novel pediatric embryonal tumor with a ZNF532::NUTM1 fusion

Optical genome mapping identifies a novel pediatric embryonal tumor with a ZNF532::NUTM1 fusion

Optical Genome Mapping Identifies a Novel Pediatric Embryonal Tumor Subtype with a ZNF532-NUTM1 Fusion

Optical Genome Mapping Identifies a Novel Pediatric Embryonal Tumor Subtype with a ZNF532-NUTM1 Fusion

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