Novel BRD4-NUT fusion isoforms increase the pathogenic complexity in NUT midline carcinoma

Oncogene

Volumn 32, Issue 39, 2013, Pages 4664-4674

  Thompson Wicking, K ^a   Francis, R W ^a   Stirnweiss, A ^a   Ferrari, E ^a   Welch, M D ^a   Baker, E ^b   Murch, A R ^b,c   Gout, A M ^a   Carter, K W ^a   Charles, A K ^c,d   Phillips, M B ^e   Kees, U R ^a   Beesley, A H ^a  

^a UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^b KING EDWARD MEMORIAL HOSPITAL   (Australia)

^c UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^d PATHWEST LABORATORY MEDICINE   (Australia)

^e PRINCESS MARGARET HOSPITAL FOR CHILDREN   (Australia)

Author keywords

BRD4; carcinoma; NMC; NUT; RNA Seq; transcriptome

Indexed keywords

BRD4 PROTEIN; CISPLATIN; DOCETAXEL; DOXORUBICIN; FLUOROURACIL; IFOSFAMIDE; NUCLEAR PROTEIN; NUT PROTEIN; RAZOXANE; UNCLASSIFIED DRUG;

ADOLESCENT; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER RADIOTHERAPY; CANCER RECURRENCE; CARCINOMA; CARDIOTOXICITY; CASE REPORT; COUGHING; DISEASE SEVERITY; FEMALE; FEVER; GENETIC VARIABILITY; HEART PROTECTION; HEART VENTRICLE FUNCTION; HUMAN; KARYOTYPE 46,XX; MEDIASTINUM MASS; NUCLEAR PROTEIN IN TESTIS MIDLINE CARCINOMA; PRIORITY JOURNAL; RNA SPLICING; THORAX PAIN;

ADOLESCENT; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BASE SEQUENCE; CARCINOMA; CELL DIFFERENTIATION; CELL LINE, TUMOR; CELL SIZE; CHILD; CHROMOSOMES, HUMAN, PAIR 15; CHROMOSOMES, HUMAN, PAIR 19; DRUG RESISTANCE, NEOPLASM; EXONS; FATAL OUTCOME; FEMALE; HUMANS; IN SITU HYBRIDIZATION, FLUORESCENCE; LUNG NEOPLASMS; MOLECULAR SEQUENCE DATA; NUCLEAR PROTEINS; ONCOGENE PROTEINS, FUSION; PROTEIN ISOFORMS; PROTEIN STRUCTURE, SECONDARY; RNA INTERFERENCE; RNA, SMALL INTERFERING; SEQUENCE ALIGNMENT; SEQUENCE HOMOLOGY, NUCLEIC ACID; THYMUS NEOPLASMS; TRANSLOCATION, GENETIC; YOUNG ADULT;

EID: 84884902702     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2012.487     Document Type: Article

References (30)

1. French CA. Pathogenesis of NUT midline carcinoma. Annu Rev Pathol 2012; 7: 247265.
2. French CA, Ramirez CL, Kolmakova J, Hickman TT, Cameron MJ, Thyne ME et al. BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells. Oncogene 2008; 27: 22372242.
3. Shehata BM, Steelman CK, Abramowsky CR, Olson TA, French CA, Saxe DF et al. NUT midline carcinoma in a newborn with multiorgan disseminated tumor and a 2-year-old with a pancreatic/hepatic primary. Pediatr Dev Pathol 2010; 13: 481485.
4. French CA. Demystified molecular pathology of NUT midline carcinomas. J Clin Pathol 2010; 63: 492496.
5. Kees UR, Mulcahy MT, Willoughby ML. Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19). Am J Pediatr Hematol Oncol 1991; 13: 459464.
6. Kubonishi I, Takehara N, Iwata J, Sonobe H, Ohtsuki Y, Abe T et al. Novel t(15;19)(q15;p13) chromosome abnormality in a thymic carcinoma. Cancer Res 1991; 51: 33273328.
7. Kuzume T, Kubonishi I, Takeuchi S, Takeuchi T, Iwata J, Sonobe H et al. Establishment and characterization of a thymic carcinoma cell line (Ty-82) carrying t(15;19)(q15;p13) chromosome abnormality. Int J Cancer 1992; 50: 259264.
8. Bauer D, Mitchell C, Strait K, Lathan C, Stelow E, Lueer S et al. Clinicopathologic features and long-term outcomes of NUT midline carcinoma. Clin Cancer Res 2012; 18: 57735779.
9. French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA et al. Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 2004; 22: 41354139.
10. Reynoird N, Schwartz BE, Delvecchio M, Sadoul K, Meyers D, Mukherjee C et al. Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains. EMBO J 2010; 29: 29432952.
11. Schwartz BE, Hofer MD, Lemieux ME, Bauer DE, Cameron MJ, West NH et al. Differentiation of NUT midline carcinoma by epigenomic reprogramming. Cancer Res 2011; 71: 26862696.
12. Toretsky JA, Jenson J, Sun CC, Eskenazi AE, Campbell A, Hunger SP et al. Translocation (11;15;19): a highly specific chromosome rearrangement associated with poorly differentiated thymic carcinoma in young patients. Am J Clin Oncol 2003; 26: 300306.
13. Vargas SO, French CA, Faul PN, Fletcher JA, Davis IJ, Dal Cin P et al. Upper respiratory tract carcinoma with chromosomal translocation 15;19: evidence for a distinct disease entity of young patients with a rapidly fatal course. Cancer 2001; 92: 11951203.
14. Haack H, Johnson LA, Fry CJ, Crosby K, Polakiewicz RD, Stelow EB et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody. Am J Surg Pathol 2009; 33: 984991.
15. French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P et al. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol 2001; 159: 19871992.
16. French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res 2003; 63: 304307.
17. Tanaka M, Kato K, Gomi K, Yoshida M, Niwa T, Aida N et al. NUT midline carcinoma: Report of 2 Cases Suggestive of Pulmonary Origin. Am J Surg Pathol 2012; 36: 381388.
18. Engleson J, Soller M, Panagopoulos I, Dahlen A, Dictor M, Jerkeman M. 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 2006; 6: 69.
19. Haruki N, Kawaguchi KS, Eichenberger S, Massion PP, Gonzalez A, Gazdar AF et al. Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro. J Med Genet 2005; 42: 558564.
20. Francis RW, Thompson-Wicking K, Carter KW, Anderson D, Kees UR, Beesley AH. FusionFinder: a software tool to identify expressed gene fusion candidates from RNA-Seq data. PLoS One 2012; 7: e39987.
21. Yan J, Diaz J, Jiao J, Wang R, You J. Perturbation of BRD4 protein function by BRD4-NUT protein abrogates cellular differentiation in NUT midline carcinoma. J Biol Chem 2011; 286: 2766327675.
22. Mertens F, Wiebe T, Adlercreutz C, Mandahl N, French CA. Successful treatment of a child with t(15;19)-positive tumor. Pediatr Blood Cancer 2007; 49: 10151017.
23. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O et al. Selective inhibition of BET bromodomains. Nature 2010; 468: 10671073.
24. Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 2011; 478: 529533.
25. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011; 478: 524528.
26. Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T et al. BET bromodomain inhibition targets both c-MYC and IL7R in high-risk acute lymphoblastic leukemia. Blood 2012; 120: 28432852.
27. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011; 146: 904917.
28. Prinjha RK, Witherington J, Lee K. Place your BETs: the therapeutic potential of bromodomains. Trends Pharmacol Sci 2012; 33: 146153.
29. Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer 2012; 12: 465477.
30. Trapnell C, Pachter L, Salzberg SL. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 2009; 25: 11051111.