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. 2005 Jul;42(7):558–564. doi: 10.1136/jmg.2004.029686

Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro

N Haruki 1, K Kawaguchi 1, S Eichenberger 1, P Massion 1, A Gonzalez 1, A Gazdar 1, J Minna 1, D Carbone 1, T Dang 1
PMCID: PMC1736105  PMID: 15994877

Abstract

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.

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Selected References

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