Analysis of genetic stability at the EP300 and CREBBP loci in a panel of cancer cell lines.
EP300 (p300) and CREBBP (CBP) are highly related transcriptional co-activators possessing histone acetyltransferase activity. These proteins have been implicated in coordinating numerous transcriptional responses that are important in the processes of proliferation and differentiation. A role for EP300 and CREBBP as tumor suppressors in cancer has been suggested by the fact that they are targeted by viral oncogenes; there is an increased incidence of hematologic malignancies in mice monoallelic for CREBBP; and loss, albeit at a low frequency, of both EP300 alleles in epithelial cancers has been observed. Because the level of EP300/CREBBP appears to have a critical effect on integrating certain transcriptional processes, we sought to determine whether a loss in the combined gene dosage of EP300 and CREBBP might play a role in cancer. Accordingly, we screened a panel of 103 cell lines for loss of heterozygosity and found 35 and 51% LOH for the CREBBP and EP300 loci, respectively. Concordant loss of CREBBP and EP300 was not associated with mutations in important regions of the remaining EP300 or CREBBP genes. In addition, there did not appear to be a statistically significant selection in cancer cells, stratified by various criteria, for the concordant loss of EP300 and CREBBP. We conclude that EP300 and CREBBP rarely act as classical tumor suppressors in human cancer.
Tillinghast
Guy W
GW
Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Partee
Jason
J
Albert
Paul
P
Kelley
Jenny M
JM
Burtow
Kenneth H
KH
Kelly
Kathleen
K
D050882:CREB-Binding Protein; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D020014:K562 Cells; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005819:Genetic Markers; D009687:Nuclear Proteins; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494363:CREBBP protein, human