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Anti-NUT (clone QR043)

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.

    • [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.

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