Farhad Motavalli Khiavi1,2, Maryam Nasimi3, Hamzeh Rahimi4. 1. Department of Virology, Pasteur Institute of Iran, Tehran, Iran. 2. Medical Biotechnology Research Center, AJA University of Medical Sciences, Tehran, Iran. 3. Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran, narvan.nasimi@gmail.com. 4. Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran.
Abstract
INTRODUCTION: The presence of Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma (MCC). However, there was sparse information on the link of other common nonmelanoma skin cancers - basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - to MCPyV infection. The current study describes the phylogenetic information of MCPyV isolated from Iranian non-MCC (nonmelanoma skin cancers) focusing on tumorigenesis of mutations in large tumor (LT) antigen (LT-Ag) fragment. METHODS: Sixty patients with BCC and 20 patients with SCC were included in this study (48 males and 32 females; average age 65 years). The MCPyV-DNA copy number in positive samples was measured by quantitative real-time PCR. Then, mutational analysis of the MCPyV LT gene was carried out by direct sequencing. RESULTS: While MCPyV DNA was detected in 6 (10%) of 60 BCC samples, no viral genome was found in SCCs. There was no distinct association of MCPyV positivity with gender, age, or type of tumor (BCC or SCC) (p value >0.05). Quantitative real-time PCR revealed that the median number of viral DNA copies per cell was 0.7 in 6 MCPyV-positive BCC samples. Furthermore, full-length LT-Ag sequencing of positive samples indicated no stop codon or frameshift mutations compared to reference sequences. CONCLUSION: Considering the important role of the LT-Ag in the pathogenicity of MCPyV, non-synonymous mutations compared with the reference proteins triggered relevant amino acid substitutions. Overall, the results showed no tumor-associated mutations in the LT-Ag sequence of MCPyVs from positive samples.
INTRODUCTION: The presence of Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma (MCC). However, there was sparse information on the link of other common nonmelanoma skin cancers - basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - to MCPyV infection. The current study describes the phylogenetic information of MCPyV isolated from Iranian non-MCC (nonmelanoma skin cancers) focusing on tumorigenesis of mutations in large tumor (LT) antigen (LT-Ag) fragment. METHODS: Sixty patients with BCC and 20 patients with SCC were included in this study (48 males and 32 females; average age 65 years). The MCPyV-DNA copy number in positive samples was measured by quantitative real-time PCR. Then, mutational analysis of the MCPyV LT gene was carried out by direct sequencing. RESULTS: While MCPyV DNA was detected in 6 (10%) of 60 BCC samples, no viral genome was found in SCCs. There was no distinct association of MCPyV positivity with gender, age, or type of tumor (BCC or SCC) (p value >0.05). Quantitative real-time PCR revealed that the median number of viral DNA copies per cell was 0.7 in 6 MCPyV-positive BCC samples. Furthermore, full-length LT-Ag sequencing of positive samples indicated no stop codon or frameshift mutations compared to reference sequences. CONCLUSION: Considering the important role of the LT-Ag in the pathogenicity of MCPyV, non-synonymous mutations compared with the reference proteins triggered relevant amino acid substitutions. Overall, the results showed no tumor-associated mutations in the LT-Ag sequence of MCPyVs from positive samples.
Authors: John Charles Rotondo; Chiara Mazziotta; Carmen Lanzillotti; Mauro Tognon; Fernanda Martini Journal: Int J Mol Sci Date: 2021-10-24 Impact factor: 5.923