Mutation analysis of EP300 in colon, breast and ovarian carcinomas

• Published in: International journal of cancer Vol. 102; no. 2; pp. 137 - 141
• Main Authors: Bryan, Emma J., Jokubaitis, Venta J., Chamberlain, Narelle L., Baxter, Simon W., Dawson, Elisabeth, Choong, David Y.H., Campbell, Ian G.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 10.11.2002; Wiley-Liss
• Subjects: Acetyltransferases - genetics; Biological and medical sciences; breast cancer; Breast Neoplasms - genetics; cancer cell lines; colon cancer; Colonic Neoplasms - genetics; DNA Mutational Analysis; EP300; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, Tumor Suppressor; Gynecology. Andrology. Obstetrics; Histone Acetyltransferases; Humans; Loss of Heterozygosity; Mammary gland diseases; Medical sciences; Mutation; ovarian cancer; Ovarian Neoplasms - genetics; Saccharomyces cerevisiae Proteins - genetics; somatic mutations; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Cells, Cultured; Tumors; tumour suppressor; Human; Carcinoma; Etiopathogenesis; Malignant tumor; Experimental study; Carcinogenesis; Female genital diseases; Colonic disease; Polymerase chain reaction; Mammary gland diseases; Ovarian diseases; Ovary; Cell line; Biopsy; Analysis; Immunoblotting assay; Digestive diseases; Intestinal disease; Colon; Mammary gland; Mutation; Molecular biology
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.10682

The putative tumour suppressor gene EP300 is located on chromosome 22q13 which is a region showing frequent loss of heterozygosity (LOH) in colon, breast and ovarian cancers. We analysed 203 human breast, colon and ovarian primary tumours and cell lines for somatic mutations in EP300. LOH across the EP300 locus was detected in 38% of colon, 36% of breast, and 49% of ovarian primary tumours but no somatic mutations in EP300 were identified in any primary tumour. Analysis of 17 colon, 11 breast, and 11 ovarian cancer cell lines identified truncating mutations in 4 colon cancer cell lines (HCT116, HT29, LIM2405 and LIM2412). We confirmed the presence of a previously reported frameshift mutation in HCT116 at codon 1699 and identified a second frameshift mutation at codon 1468. Bi‐allelic inactivation of EP300 was also detected in LIM2405 that harbours an insC mutation at codon 927 as well an insA mutation at codon 1468. An insA mutation at codon 1468 was identified in HT29 and a CGA>TGA mutation at codon 86 was identified in LIM2412. Both these lines were heterozygous across the EP300 locus and western blot analysis confirmed the presence of an apparently wild‐type protein. Our study has established that genetic inactivation of EP300 is rare in primary colorectal, breast and ovarian cancers. In contrast, mutations are common among colorectal cancer cell lines with 4/17 harbouring homozygous or heterozygous mutations. The rarity of EP300 mutations among these tumour types that show a high frequency of LOH across 22q13 may indicate that another gene is the target of the loss. It is possible that bi‐allelic inactivation of EP300 is not necessary and that haploinsufficiency is sufficient to promote tumorigenesis. Alternatively, silencing of EP300 may be achieved by epigenetic mechanisms such as promoter methylation. © 2002 Wiley‐Liss, Inc.