NUT midline carcinoma (NMC) is a rare neoplasm with a poor prognosis and involving mostly young patients. Here we describe a classic NMC with a BRD4-NUT fusion gene in a middle-aged woman. We also analyzed some biological features that could potentially influence its clinical behavior such as HPV infection, EWSR1 rearrangement, and the status of the EGFR gene.
FrenchC.A., MiyoshiI., AsterJ.C., KubonishiI., KrollT.G., Dal CinP., VargasS.O., Perez-AtaydeA.R., FletcherJ.A.: BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19).Am J Pathol, 159: 1987–1992, 2001.
2.
ThwayK., RockcliffeS., GonzalezD., SwansburyJ., MinT., ThompsonL., FisherC.: Utility of sarcoma-specific fusion gene analysis in paraffin-embedded material for routine diagnosis at a specialist centre.J Clin Pathol, 63: 508–512, 2010.
3.
HolladayE.B., LoganS., ArnoldJ., KneselB., SmithG.D.: A comparison of the clinical utility of p16(INK4a) immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia.Cancer, 108: 451–446, 2006.
4.
HsiehM.S., FrenchC.A., LiangC.W., HsiaoC.H.: NUT midline carcinoma: case report and review of the literature.Int J Surg Pathol, 19: 808–812, 2011.
5.
ZiaiJ., FrenchC.A., ZambranoE.: NUT gene rearrangement in a poorly-differentiated carcinoma of the submandibular gland.Head Neck Pathol, 4: 163–168, 2010.
6.
FrenchC.A., RamirezC.L., KolmakovaJ., HickmanT.T., CameronM.J., ThyneM.E., KutokJ.L., ToretskyJ.A., TadavarthyA.K., KeesU.R., FletcherJ.A., AsterJ.C.: BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells.Oncogene, 27: 2237–2242, 2008.
StelowE.B., FrenchC.A.: Carcinomas of the upper aerodigestive tract with rearrangement of the nuclear protein of the testis (NUT) gene (NUT midline carcinoma).Adv Anat Pathol, 16: 92–96, 2009.
HaackH., JohnsonL.A., FryC.J., CrosbyK., PolakiewiczR.D., StelowE.B., HongS.M., SchwartzB.E., CameronM.J., RubinM.A., ChangM.C., AsterJ.C., FrenchC.A.: Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody.Am J Surg Pathol, 33: 984–991, 2009.
11.
EnglesonJ., SollerM., PanagopoulosI., DahlénA., DictorM., JerkemanM.: Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy.BMC Cancer, 16: 69, 2006.
ReynoirdN., SchwartzB.E., DelvecchioM., SadoulK., MeyersD., MukherjeeC., CaronC., KimuraH., RousseauxS., ColeP.A., PanneD., FrenchC.A., KhochbinS.: Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains.EMBO J, 29: 2943–2952, 2010.
14.
JangM.K., MochizukiK., ZhouM., JeongH.S., BradyJ.N., OzatoK.: The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription.Mol Cell, 19: 523–534, 2005.
15.
MochizukiK., NishiyamaA., JangM.K., DeyA., GhoshA., TamuraT., NatsumeH., YaoH., OzatoK.: The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase.J Biol Chem, 283: 9040–9048, 2008.
16.
YangZ., YikJ.H., ChenR., HeN., JangM.K., OzatoK., ZhouQ.: Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4.Mol Cell, 19: 535–545, 2005.
FrenchC.A., KutokJ.L., FaquinW.C., ToretskyJ.A., AntonescuC.R., GriffinC.A., NoseV., VargasS.O., MoschoviM., Tzortzatou-StathopoulouF., MiyoshiI., Perez-AtaydeA.R., AsterJ.C., FletcherJ.A.: Midline carcinoma of children and young adults with NUT rearrangement.J Clin Oncol, 22: 4135–4139, 2004.
19.
CiardielloF., TortoraG.: EGFR antagonists in cancer treatment.N Engl J Med, 358: 1160–1174, 2008.
20.
LeemansC.R., BraakhuisB.J., BrakenhoffR.H.: The molecular biology of head and neck cancer.Nat Rev Cancer, 11: 9–22, 2011.
21.
BhaijeeF., PepperD.J., PitmanK.T., BellD.: New developments in the molecular pathogenesis of head and neck tumors: a review of tumor-specific fusion oncogenes in mucoepidermoid carcinoma, adenoid cystic carcinoma, and NUT midline carcinoma.Ann Diagn Pathol, 15: 69–77, 2011.
