P53 deregulation in Epstein-Barr virus-associated gastric cancer

TP53 is a tumour suppressor gene frequently mutated in human cancers; nevertheless, in EBV-associated malignancies mutations are uncommon despite frequent deregulation of the p53 pathway. In this study, we aimed to investigate p53 expression, TP53 mRNA levels and TP53 mutations in EBV-associated gas...

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Bibliographic Details
Published in:	Cancer letters 2017-09, Vol.404, p.37-43
Main Authors:	Ribeiro, Joana, Malta, Mariana, Galaghar, Ana, Silva, Fernanda, Afonso, Luís Pedro, Medeiros, Rui, Sousa, Hugo
Format:	Article
Language:	eng
Subjects:	Adult Aged Aged, 80 and over Antigens Apoptosis Bacterial infections Cancer Carcinoma Case-Control Studies Deoxyribonucleic acid Deregulation DNA DNA sequencing EBV-associated gastric cancer EBVaGC Epstein-Barr virus Epstein-Barr Virus Infections - genetics Epstein-Barr Virus Infections - metabolism Espstein-Barr virus Female Gastric cancer Gene expression Gene Expression Regulation, Neoplastic Genes, p53 Genomes Guanylate cyclase Herpesvirus 4, Human Humans Immunohistochemistry Infections Male Middle Aged Missense mutation mRNA Mutation p53 p53 Protein Proteins RNA, Messenger - metabolism Stomach cancer Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - virology Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors Viruses
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Summary:	TP53 is a tumour suppressor gene frequently mutated in human cancers; nevertheless, in EBV-associated malignancies mutations are uncommon despite frequent deregulation of the p53 pathway. In this study, we aimed to investigate p53 expression, TP53 mRNA levels and TP53 mutations in EBV-associated gastric carcinoma (EBVaGC). A case-control study was performed using 46 patients: 15 EBVaGC and 31 EBV-negative GC (EBVnGC) cases. p53 expression was detected by immunohistochemistry (IHC), the evaluation of p53 mRNA levels was performed by RT-qPCR and TP53 mutations were investigated only in EBVaGC cases using the DNA sanger sequencing method. p53 expression was found in 97.8% (45/46) of all gastric cancer cases (including EBVaGC and EBVnGC groups). Despite the high frequency of p53 expression in both groups, the percentages of cells are significantly higher among EBVaGC cases (p = 0.027). Regarding the mRNA levels, we found a significantly increased expression of p53 mRNA in EBVnGC (2−ΔΔCt = 13.4 ± 2.4; p = 0.0029) when compared with EBVaGC. Furthermore, the sequencing analysis of TP53 gene revealed that only one of the 15 EBVaGC cases presented a missense mutation. Our results demonstrated that EBV-associated gastric carcinomas are characterized by a significant decrease of TP53 mRNA levels with a strong p53 expression and rare TP53 mutations when compared with EBV-negative cancers. Considering these results, EBV seems to induce a stabilization of p53 in the EBVaGC independently of the presence of mutations, which remains to be explained. •EBVaGCs are characterized by a significant decrease of TP53 mRNA with a strong p53 expression.•TP53 mutations are a rare event in EBV-associated gastric cancer.•p53 stabilization takes place in EBV-induced gastric carcinogenesis.
ISSN:	0304-3835 1872-7980