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 EP...

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Bibliographic Details
Published in:Genes chromosomes & cancer 2003-06, Vol.37 (2), p.121-131
Main Authors: Tillinghast, Guy W., Partee, Jason, Albert, Paul, Kelley, Jenny M., Burtow, Kenneth H., Kelly, Kathleen
Format: Article
Language:English
Subjects:
Chromosome Aberrations
CREB-Binding Protein
DNA Mutational Analysis - methods
DNA, Neoplasm - analysis
Female
Genes, Neoplasm - genetics
Genetic Markers - genetics
HL-60 Cells
HT29 Cells
Humans
K562 Cells
Loss of Heterozygosity - genetics
Male
Microsatellite Repeats - genetics
Nuclear Proteins - genetics
Trans-Activators - genetics
Tumor Cells, Cultured
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Summary: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. Published 2003 Wiley‐Liss, Inc.
ISSN:1045-2257
1098-2264
DOI:10.1002/gcc.10195