P53 deregulation in Epstein-Barr virus-associated gastric cancer

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Ribeiro, J (Author) Other; Malta, M (Author) Other; Galaghar, A (Author) Other; Silva, F (Author) Other; Afonso, LP (Author) Other; Rui Medeiros (Author) ICBAS; Sousa, H (Author) Other

Journal

Title: Cancer Letters

Vol. 404

Pages: 37-43

ISSN: 0304-3835

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 25 Citations

Scopus - 27 Citations

Other information

Authenticus ID: P-00M-WYK

DOI: 10.1016/j.canlet.2017.07.010

Abstract (EN): 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(-Delta Delta ct) = 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7