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


CONCLUSIONS
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.
Haruki
N
N
Department of Surgery, Nagoya City Hospital, Nagoya, Japan.
Kawaguchi
K S
KS
Eichenberger
S
S
Massion
P P
PP
Gonzalez
A
A
Gazdar
A F
AF
Minna
J D
JD
Carbone
D P
DP
Dang
T P
TP
D000328:Adult; D015152:Blotting, Northern; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics*; D014162:Transfection; D014178:Translocation, Genetic / Q000235:genetics*
C471990:BRD4-NUT fusion oncogene protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion