Related Experiment Video
Updated: May 28, 2026
08:59
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Pathogenesis of NUT midline carcinoma
1Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. cfrench@partners.org
Annual Review of Pathology
|October 25, 2011
Summary
NUT midline carcinoma (NMC) is a rare, aggressive cancer defined by NUT gene rearrangements. BET inhibitors can induce differentiation, offering a targeted therapy approach for this challenging disease.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- NUT midline carcinoma (NMC) is an aggressive squamous cell carcinoma characterized by NUT gene rearrangements, often forming BRD4-NUT fusions.
- NMC can occur at any age and may be misdiagnosed as common squamous cell carcinomas.
- The disease exhibits genomic instability, suggesting a unique pathogenic pathway.
Purpose of the Study:
- To elucidate the underlying mechanisms of NMC pathogenesis.
- To identify potential targeted therapeutic strategies for NMC.
Main Methods:
- Analysis of chromosomal rearrangements involving the NUT gene.
- Investigation of the mechanistic role of BRD-NUT fusion proteins in cellular differentiation.
- Evaluation of the efficacy of BET inhibitors and histone deacetylase inhibitors in inducing NMC cell differentiation.
Main Results:
- BRD-NUT fusion proteins were identified as key drivers, potentially by inhibiting histone acetyltransferase activity and blocking differentiation.
- BET inhibitors demonstrated the ability to induce terminal differentiation in NMC cells by disrupting BRD-NUT protein binding to chromatin.
- Histone deacetylase inhibitors also showed potential in inducing differentiation.
Conclusions:
- NMC pathogenesis involves a distinct genetic pathway characterized by NUT gene rearrangements.
- Targeted therapies, specifically BET inhibitors, show promise for treating NMC due to their ability to induce differentiation in cancer cells.
- These findings offer a rationale for developing novel therapeutic strategies for NMC, which is typically resistant to conventional treatments.
Related Concept Videos
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:30Metastasis
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...