Contribution of the BOP1 gene, located on 8q24, to colorectal tumorigenesis.
The most common form of genomic instability observed in colorectal cancer is chromosomal instability (CIN), whose molecular bases remain to be determined. We have previously demonstrated that inactivation in human cells of several components of the Pes1-Bop1 complex (BOP1, GRWD1, PES1, ORC6L, and RPL3), involved in ribosome biogenesis, altered chromosome segregation. To determine the contribution to colorectal tumorigenesis of somatic alterations of genes involved in ribosome biogenesis, we screened 56 primary colorectal cancers, using quantitative multiplex PCR of short fluorescent fragments, a sensitive method for the detection of gene dosage alterations. We found that dosage increase of the BOP1 gene was a frequent event, being detected in 39% of the tumors, and we show that it is associated with an increase of BOP1 mRNA. Scanning of 8q24, on which BOP1 is located, revealed that in colorectal cancers, gene dosage increase of BOP1 can be independent from that of MYC and was more frequent than that affecting MYC. Finally, transient overexpression of BOP1 in human cells increased the percentage of multipolar spindles. Together with our previous results, the present study strongly suggests that deregulation of the BOP1 pathway contributes to colorectal tumorigenesis.
Killian
Audrey
A
INSERM U614, Faculté de Médecine et de Pharmacie, 22 Boulevard Gambetta, 76183 Rouen, France.
Sarafan-Vasseur
Nasrin
N
Sesboüé
Richard
R
Le Pessot
Florence
F
Blanchard
France
F
Lamy
Aude
A
Laurent
Michelle
M
Flaman
Jean-Michel
JM
Frébourg
Thierry
T
D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics*; D018628:Gene Dosage; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D000090822:Ribosomal Protein L3; D015398:Signal Transduction / Q000235:genetics*
C514383:BOP1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C000716547:RPL3 protein, human; D000090822:Ribosomal Protein L3