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NUT midline carcinoma

Tuesday 5 May 2009

Definition: NUT midline carcinoma (NMC) is a high-grade malignancy that is defined by rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14.

NMCs are morphologically indistinguishable from other poorly differentiated carcinomas, and the diagnosis is usually made currently by fluorescence in situ hybridization (FISH).

Synopsis

- poorly differentiated carcinoma

Cytogenetics

- t(15;19) translocation.

Localization

- tonsils (21922980)
- mediastinum (20395873, 22790861)
- submandibular gland (20352379)
- parotid gland (19561446)
- pancreas/liver (20017639)
- upper aerodigestive tract (18391746)

Variants

- neonatal forms (20017639)

Immunochemistry

IHC staining with the C52 monoclonal antibody is a highly sensitive and specific test that reliably distinguishes NMC from other forms of carcinoma. (19363441)

Molecular biology

- BRD4-NUT gene fusion (16542442)

Reviews

- A review of NUT midline carcinoma. Stelow EB. Head Neck Pathol. 2011 Mar;5(1):31-5. PMID: 21221870

- NUT midline carcinoma. French CA. Cancer Genet Cytogenet. 2010 Nov;203(1):16-20. Review. PMID: 20951314

Open references

- NUT gene rearrangement in a poorly-differentiated carcinoma of the submandibular gland. Ziai J, French CA, Zambrano E. Head Neck Pathol. 2010 Jun;4(2):163-8. PMID: 20352379 [Free]

- Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy. Engleson J, Soller M, Panagopoulos I, Dahlén A, Dictor M, Jerkeman M. BMC Cancer. 2006 Mar 16;6:69. PMID: 16542442 [Free]

References

- Pathologic Characteristics of NUT Midline Carcinoma Arising in the Mediastinum. Evans AG, French CA, Cameron MJ, Fletcher CD, Jackman DM, Lathan CS, Sholl LM. Am J Surg Pathol. 2012 Aug;36(8):1222-7. PMID: 22790861

- Perturbation of BRD4 protein function by BRD4-NUT protein abrogates cellular differentiation in NUT midline carcinoma. Yan J, Diaz J, Jiao J, Wang R, You J. J Biol Chem. 2011 Aug 5;286(31):27663-75. PMID: 21652721

- Differentiation of NUT midline carcinoma by epigenomic reprogramming. Schwartz BE, Hofer MD, Lemieux ME, Bauer DE, Cameron MJ, West NH, Agoston ES, Reynoird N, Khochbin S, Ince TA, Christie A, Janeway KA, Vargas SO, Perez-Atayde AR, Aster JC, Sallan SE, Kung AL, Bradner JE, French CA. Cancer Res. 2011 Apr 1;71(7):2686-96. PMID: 21447744 [Free]

- Diagnosis of NUT Midline Carcinoma Using a NUT-specific Monoclonal Antibody. Haack H, Johnson LA, Fry CJ, Crosby K, Polakiewicz RD, Stelow EB, Hong SM, Schwartz BE, Cameron MJ, Rubin MA, Chang MC, Aster JC, French CA. Am J Surg Pathol. 2009 Apr 9. PMID: 19363441

- Molecular pathology of NUT midline carcinomas. French CA. J Clin Pathol. 2008 Jun 13. PMID: 18552174

- BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells. French CA, Ramirez CL, Kolmakova J, Hickman TT, Cameron MJ, Thyne ME, Kutok JL, Toretsky JA, Tadavarthy AK, Kees UR, Fletcher JA, Aster JC. Oncogene. 2008 Apr 3;27(15):2237-42. PMID: 17934517

- NUT midline carcinoma of the parotid gland with mesenchymal differentiation. den Bakker MA, Beverloo BH, van den Heuvel-Eibrink MM, Meeuwis CA, Tan LM, Johnson LA, French CA, van Leenders GJ. Am J Surg Pathol. 2009 Aug;33(8):1253-8. PMID: 19561446

- NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract. Stelow EB, Bellizzi AM, Taneja K, Mills SE, Legallo RD, Kutok JL, Aster JC, French CA. Am J Surg Pathol. 2008 Jun;32(6):828-34. PMID: 18391746

- Recurrent fusion oncogenes in carcinomas. Teixeira MR. Crit Rev Oncog. 2006 Dec;12(3-4):257-71. PMID: 17425505

- Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy. Engleson J, Soller M, Panagopoulos I, Dahlén A, Dictor M, Jerkeman M. BMC Cancer. 2006 Mar 16;6:69. PMID: 16542442

- Successful treatment of a child with t(15;19)-positive tumor. Mertens F, Wiebe T, Adlercreutz C, Mandahl N, French CA. Pediatr Blood Cancer. 2007 Dec;49(7):1015-7. PMID: 16435379

- Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro. Haruki N, Kawaguchi KS, Eichenberger S, Massion PP, Gonzalez A, Gazdar AF, Minna JD, Carbone DP, Dang TP. J Med Genet. 2005 Jul;42(7):558-64. PMID: 15994877

- Midline carcinoma of children and young adults with NUT rearrangement. French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, Nose V, Vargas SO, Moschovi M, Tzortzatou-Stathopoulou F, Miyoshi I, Perez-Atayde AR, Aster JC, Fletcher JA. J Clin Oncol. 2004 Oct 15;22(20):4135-9.
PMID: 15483023

- BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. Cancer Res. 2003 Jan 15;63(2):304-7. PMID: 12543779

- The cytologic features of NUT midline carcinoma. Bellizzi AM, Bruzzi C, French CA, Stelow EB. Cancer Cytopathol. 2009 Sep 30. PMID: 19795508

- NUT midline carcinoma of the parotid gland with mesenchymal differentiation. den Bakker MA, Beverloo BH, van den Heuvel-Eibrink MM, Meeuwis CA, Tan LM, Johnson LA, French CA, van Leenders GJ. Am J Surg Pathol. 2009 Aug;33(8):1253-8. PMID: 19561446

- Carcinomas of the upper aerodigestive tract with rearrangement of the nuclear protein of the testis (NUT) gene (NUT midline carcinomas). Stelow EB, French CA. Adv Anat Pathol. 2009 Mar;16(2):92-6. PMID: 19550370

- Diagnosis of NUT Midline Carcinoma Using a NUT-specific Monoclonal Antibody. Haack H, Johnson LA, Fry CJ, Crosby K, Polakiewicz RD, Stelow EB, Hong SM, Schwartz BE, Cameron MJ, Rubin MA, Chang MC, Aster JC, French CA. Am J Surg Pathol. 2009 Jul;33(7):984-91. PMID: 19363441

- Molecular pathology of NUT midline carcinomas. French CA. J Clin Pathol. 2008 Jun 13. PMID: 18552174

- NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract. Stelow EB, Bellizzi AM, Taneja K, Mills SE, Legallo RD, Kutok JL, Aster JC, French CA. Am J Surg Pathol. 2008 Jun;32(6):828-34. PMID: 18391746

- BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells. French CA, Ramirez CL, Kolmakova J, Hickman TT, Cameron MJ, Thyne ME, Kutok JL, Toretsky JA, Tadavarthy AK, Kees UR, Fletcher JA, Aster JC. Oncogene. 2008 Apr 3;27(15):2237-42. PMID: 17934517

- Recurrent fusion oncogenes in carcinomas. Teixeira MR. Crit Rev Oncog. 2006 Dec;12(3-4):257-71. PMID: 17425505

- Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy. Engleson J, Soller M, Panagopoulos I, Dahlén A, Dictor M, Jerkeman M. BMC Cancer. 2006 Mar 16;6:69. PMID: 16542442

- Midline carcinoma of children and young adults with NUT rearrangement. French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, Nose V, Vargas SO, Moschovi M, Tzortzatou-Stathopoulou F, Miyoshi I, Perez-Atayde AR, Aster JC, Fletcher JA. J Clin Oncol. 2004 Oct 15;22(20):4135-9. PMID: 15483023

- BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. Cancer Res. 2003 Jan 15;63(2):304-7. PMID: 12543779