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Mutations truncating the EP300 acetylase in human cancers
S A Gayther1, S J Batley, L Linger
1Department of Oncology, University of Cambridge, Cambridge, UK.
Nature Genetics
|March 4, 2000
Summary
The EP300 gene, a histone acetyltransferase, is frequently mutated in epithelial cancers. These mutations inactivate EP300, suggesting it acts as a tumor suppressor gene in cancer development.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- EP300 is a histone acetyltransferase regulating gene transcription through chromatin remodeling.
- EP300 plays a role in cell proliferation and differentiation.
- Previous studies suggested EP300's involvement in cancer due to viral oncoprotein targeting and alterations in malignancies.
Purpose of the Study:
- To investigate the role of EP300 mutations in epithelial tumorigenesis.
- To provide direct evidence for EP300's function in human cancer development.
Main Methods:
- Analysis of EP300 mutations in 193 epithelial cancers, including primary tumors and cell lines.
- Identification of truncating mutations, insertions, and missense alterations.
- Assessment of second allele inactivation in cases with truncating mutations.
Main Results:
- EP300 mutations, predicting truncated proteins, were found in 6% of analyzed epithelial cancers.
- Mutations were identified in primary colorectal and breast cancers, as well as in colorectal, breast, and pancreatic cancer cell lines.
- Second allele inactivation was observed in multiple cases, supporting EP300's tumor-suppressive role.
Conclusions:
- EP300 is somatically mutated in epithelial cancers.
- The findings provide the first direct evidence that EP300 functions as a classical tumor suppressor gene.
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