Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro.
J Med Genet
; 42(7): 558-64, 2005 Jul.
Article
em En
| MEDLINE
| ID: mdl-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 G(1) 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
/
Proteínas Nucleares
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Proteínas de Fusão Oncogênica
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Fase S
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Neoplasias Pulmonares
Limite:
Adult
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Female
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Humans
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Japão