Iranian Journal of Pathology

A Preliminary Sequence Analysis of the Epstein-Barr Virus Nuclear Antigen 1 (EBNA1) Carboxy-Terminal Region in Cervical and Ovarian Cancers

Document Type : Original Research

Authors

Fatemeh Hoseini Tabatabaie 1
Seyed Younes Hosseini 1
Seyed Mohammad Ali Hashemi 1
Akbar Safaie 2
Jamal Sarvari 1, 3

1 Department of Bacteriology & Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Gastroenterohepathology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

https://doi.org/10.30699/ijp.2023.551761.2872
Abstract
Background & Objective: Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical and ovarian cancer and healthy individuals.
Methods: As test and control groups, 18 EBV-positive paraffin-embedded samples of cervical and ovarian cancer and 10 age- and gender-matched healthy volunteers who did not have cancer but were EBV-positive were both used. Utilizing a commercial DNA extraction kit, total DNA was extracted following deparaffinization. The entire C-terminal region of the EBNA1 sequence was amplified using an in-house nested PCR. Phylogenetic analysis and Sanger sequencing were used to analyze the sequences using MEGA 7 software and through NJ method.
Results: Sequence analysis revealed that the P-Ala subtype of EBNA1 was present in all samples. In two and one samples, respectively, of cervical cancer patients, the mutations A1887G and G1891A were found. The G1595T mutation was also detected in four sequences taken from ovarian cancer patients. No statistically significant difference could be found between the frequency of mutations in patients and controls (P>0.05). No known amino acid substitutions were found in the USP7-binding region and the DBD/DD domain.
Conclusion: The findings showed that P-Ala is the predominant EBV subtype across all samples. Additionally, as the sequence of EBNA1's C-terminal region is so stable, it's possible that it had little impact on the pathogenesis of ovarian and cervical malignancies. It is advised to conduct additional research to verify these findings.

Keywords

Cervical cancer
EBNA1
Epstein-Barr virus
Mutation
Ovarian cancer

Subjects

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Iranian Journal of Pathology
Volume 18, Issue 1
Winter 2023
Pages 24-32

  • Receive Date 24 April 2022
  • Revise Date 24 July 2022
  • Accept Date 21 September 2022

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