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Merkel 细胞多瘤病毒基因表达和大肿瘤抗原在伊朗患者非 Merkel 细胞癌肿瘤中的突变分析。

Merkel Cell Polyomavirus Gene Expression and Mutational Analysis of Large Tumor Antigen in Non-Merkel Cell Carcinoma Tumors of Iranian Patients.

机构信息

Department of Virology, Pasteur Institute of Iran, Tehran, Iran.

Medical Biotechnology Research Center, AJA University of Medical Sciences, Tehran, Iran.

出版信息

Public Health Genomics. 2020;23(5-6):210-217. doi: 10.1159/000510254. Epub 2020 Sep 23.

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.

摘要

简介

Merkel 细胞多瘤病毒(MCPyV)已在 Merkel 细胞癌(MCC)中被鉴定出来。然而,关于其他常见的非黑色素瘤皮肤癌——基底细胞癌(BCC)和鳞状细胞癌(SCC)与 MCPyV 感染的联系,信息仍然很少。本研究描述了从伊朗非 MCC(非黑色素瘤皮肤癌)分离的 MCPyV 的系统发育信息,重点研究了大肿瘤(LT)抗原(LT-Ag)片段突变与肿瘤发生的关系。

方法

本研究纳入了 60 例 BCC 患者和 20 例 SCC 患者(48 名男性和 32 名女性;平均年龄 65 岁)。通过实时定量 PCR 测量阳性样本中的 MCPyV-DNA 拷贝数。然后,通过直接测序对 MCPyV LT 基因进行突变分析。

结果

虽然在 60 例 BCC 样本中有 6 例(10%)检测到 MCPyV DNA,但在 SCC 中未发现病毒基因组。MCPyV 阳性与性别、年龄或肿瘤类型(BCC 或 SCC)之间没有明显的关联(p 值>0.05)。实时定量 PCR 显示,6 例 MCPyV 阳性 BCC 样本中每细胞病毒 DNA 拷贝数的中位数为 0.7。此外,对阳性样本的全长 LT-Ag 测序表明,与参考序列相比,没有终止密码子或移码突变。

结论

考虑到 LT-Ag 在 MCPyV 致病性中的重要作用,与参考蛋白相比,非同义突变引发了相关的氨基酸取代。总体而言,结果显示 MCPyV 阳性样本的 LT-Ag 序列中没有肿瘤相关的突变。

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