Molecular determination of mutational signatures p53 and retinoblastoma (RB) in human papilloma virus-associated squamous cell carcinoma of the cervix

Abstract

Objectives: Cervical cancer is a cancer arising from the cervix due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body, of which human papilloma virus (HPV) infection causes more than 90% of cases. This study aimed at investigating the mutational signatures retinoblastoma (RB) and p53 in HPV-associated squamous cell carcinoma (SCC) of the cervix. Material and Methods: A total of 10 formalin-fixed, paraffin-embedded tissue blocks, all consisting of SCC of the cervix, were used for this study. The technique employed was nucleic acid amplification technique and various steps for DNA sequencing including DNA extraction and polymerase chain reaction. Results: Mutation in the RB gene occurred at different gene regions ranging from 10 to 230, while p53 occurred at 10–945. The most prevalent mutational signature within the RB gene regions was T>C (37.50%), while the p53 gene region was T>A (23%). Percentage mutations at single-nucleotide polymorphisms (SNPs) of RB were transition (58.8%), transversion (41.2%), Indel (0%), and substitution (0%), while point mutations were missense (65%), silent (23%), and non-sense (12%), respectively. Mutations at SNPs of p53 were transversion (47.6%), transition (38.1%), Indel (14.3%), and substitution (0%), while point mutations were missense (78%), silent (22.2%), and non-sense (0%), respectively. Conclusion: Our results indicate that the inactivation of the normal functions of the tumor-suppressor proteins RB and p53 is an important step in human cervical carcinogenesis caused by mutation or from complex formation with the HPV oncoproteins.