Anti-NUT (clone QR043)
NUT Carcinoma (NUT Carcinoma, NC) – A Rare and Aggressive Subtype of Squamous Cell Carcinoma
NUT Carcinoma (formerly NUT Midline Carcinoma, NMC) is a rare and exceptionally aggressive subtype of squamous cell carcinoma characterized by chromosomal rearrangement of the NUT gene (NUTM1, nuclear protein in testis).
Location and Epidemiology
✔ Primarily arises along the body's midline, affecting:
- Thoracic region (~50%) – chest, mediastinum, lungs
- Head and neck (~40%)
✔ Less commonly found in extramidline locations such as: - Salivary gland
- Pancreas
- Bladder
- Kidney
- Adrenal glands
- Soft tissues and bones
NUT carcinoma is almost universally fatal, with a median overall survival of 6.5 months. It can occur at any age but is most frequently diagnosed in teenagers and young adults, with a median age of 24 years.
Pathogenesis – The Role of BRD4-NUT Fusion Oncoproteins
✔ In ~75% of cases, NUT fuses with BRD4, creating the potent oncoprotein BRD4-NUT.
✔ Alternative translocations may involve NUT fusion with other partners, including:
- BRD3
- NSD3
- ZNF532
- ZNF592
✔ These fusion proteins interact with BRD4, leading to dysregulated transcription and oncogenic transformation.
Diagnosis of NUT Carcinoma
✔ Immunohistochemistry (IHC) for NUT nuclear staining is the primary diagnostic method.
✔ Molecular tests such as FISH or RT-PCR are used in ambiguous cases to confirm NUT gene translocation.
Summary
✔ NUT carcinoma is an extremely aggressive cancer, with a median survival of only 6.5 months.
✔ It predominantly affects the midline structures (thoracic region, head, and neck) but can also arise in other locations.
✔ Its pathogenesis is driven by chromosomal translocations, resulting in the expression of oncogenic BRD4-NUT fusion proteins and related variants.
✔ Diagnosis relies on immunohistochemical detection of NUT and molecular genetic analyses.
Literature
[1] Eagen KP and French CA (2021). Oncogene. 40(8):1396-1408.
[2] Hakun MC and Gu B (2021). Genes (Basel). 12(2):235.
[3] French CA (2018). Pathol Int. 68(11):583-595.
[4] Haack H et al. (2009). Am J Surg Pathol. 33(7):984-91.
Advantage of QUARTETT Antibodies
ADVANTAGES OF RECOMBINANT RABBIT MONOCLONAL ANTIBODIES
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