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Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro
  1. N Haruki1,
  2. K S Kawaguchi2,
  3. S Eichenberger2,
  4. P P Massion3,
  5. A Gonzalez4,
  6. A F Gazdar5,
  7. J D Minna5,
  8. D P Carbone2,
  9. T P Dang2
  1. 1Department of Surgery, Nagoya City Hospital, Nagoya, Japan
  2. 2Division of Hematology and Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
  3. 3Division of Allergy/Pulmonary and Critical Care, Vanderbilt University Medical Center, Nashville, TN, USA
  4. 4Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA
  5. 5Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA
  1. Correspondence to:
 T P Dang
 Vanderbilt-Ingram Cancer Center, 642 PRB, Nashville, TN 37232, USA;


Background: Somatically acquired chromosomal translocation is a common mechanism of oncogene activation in many haematopoietic tumours and sarcomas. However, very few recurrent chromosomal translocations have been reported in more common epithelial tumours such as lung carcinomas.

Methods: We established a cell line HCC2429 from an aggressive, metastatic lung cancer arising in a young, non-smoking woman, demonstrating a t(15;19)(q13.2;p13.1). The breakpoints on chromosomes 15 and 19 were cloned using long distance inverse PCR and we determined by RT-PCR that the translocation results in a novel fusion transcript in which the 3′ end Brd4 on chromosome 19p is fused to the 5′ end of NUT on chromosome 15q.

Results: In total, 128 lung cancer tissues were screened using fluorescent in situ hybridisation, but none of the tumours screened demonstrated t(15;19), suggesting that this translocation is not commonly found in lung cancer. Consistent with previous literature, ectopic expression of wild type Brd4 was shown to inhibit G1 to S progression. However, we also found that the Brd4-NUT fusion augments the inhibition of progression to S phase compared with wild type Brd4.

Conclusion: Alteration in cell cycle kinetics is important in tumorigenesis, although the exact role of Brd4-NUT fusion protein in the pathogenesis of lung cancers remains unclear and need to be further elucidated.

  • FISH, fluorescent in situ hybridisation
  • LDI-PCR, long distance inverse polymerase chain reaction
  • translocation
  • Brd4
  • lung cancer
  • fusion protein

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  • This work was supported in part by NCI Mentored Clinical Scientist Development Award (K08 CA82849), the Vanderbilt SPORE in Lung Cancer, CA90949, and a scholarship from the Naito Foundation (to N Haruki).

  • Competing interests: none declared