Evaluation of EP300 expression and mutations in pancreatic cancer

C281 The putative tumor suppressor gene EP300 encodes a histone acetyltransferase that acts as a transcriptional co-activator via chromatin remodeling and is important in the processes of cell proliferation and differentiation. A role for EP300 as a tumor suppressor in cancer has been suggested by the fact that it is targeted by viral oncogenes, and inactivating mutations have been observed in several epithelial malignancies. However, direct demonstration of the role of EP300 in tumorigenesis by inactivating mutations in pancreatic cancer has not been thoroughly investigated. To obtain a better understanding of EP300’s role in pancreatic cancer, expression of the gene was evaluated at the mRNA and protein level, using real-time RT-PCR and Western blot, respectively, in a large panel of pancreatic cancer cell lines. Prevalence of mutations in the EP300 genomic sequence in pancreatic cancer cell lines and in a set of low passage tumor xenografts was surveyed by sequencing several exons previously found to harbor inactivating mutations in other cancer types. It was found that mRNA levels of EP300 were relatively similar among the cell lines. However, a wide range of protein expression was observed. No anomalies were observed in the exons tested by sequence analysis in 21 pancreatic cancer cell lines except a previously reported deletion in PaTu8988T. Sequence analysis of 19 xenografts revealed point mutations, but no insertions or deletions that would result in a predicted truncated protein. These data suggest that truncating mutations in pancreatic cancer are probably rare, and that regulation of translation or degradation of EP300 might play a more important role in pancreatic cancer than inactivating mutations. (This work was supported by a NCI grant P01CA109552)