PDF(Pubmed)
Abstract：
Approximately 5% of colorectal cancers (CRCs) are hereditary. Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common form of recognized hereditary CRC. Although Iran, as a developing country, has a high incidence of CRC, the spectrum of variants has yet to be thoroughly investigated.
This study aimed to investigate pathogenic and non-pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS).
In the present study, 25 peripheral blood samples were collected from patients with sLS and high microsatellite instability (MSI-H). After DNA extraction, all samples underwent polymerase chain reaction and Sanger sequencing to identify the variants in the exons of MLH1 and MSH2 genes. The identified variants were interpreted using prediction tools, and were finally reported under ACMG guidelines. In our study population, 13 variants were found in the MLH1 gene and 8 in the MSH2 gene. Interestingly, 7 of the 13 MLH1 variants and 3 of the 8 MSH2 variants were novel, whereas the remaining variants were previously reported or available in databases. In addition, some patients with sLS did not have variants in the exons of the MLH1 and MSH2 genes. The variants detected in the MLH1 and MSH2 genes had specific characteristics regarding the number, area of occurrence, and their relationship with demographic and clinicopathologic features.
Overall, our results suggest that analysis of MLH1 and MSH2 genes alone is insufficient in the Iranian population, and more comprehensive tests are recommended for detecting LS.
This study aimed to investigate pathogenic and non-pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS).
In the present study, 25 peripheral blood samples were collected from patients with sLS and high microsatellite instability (MSI-H). After DNA extraction, all samples underwent polymerase chain reaction and Sanger sequencing to identify the variants in the exons of MLH1 and MSH2 genes. The identified variants were interpreted using prediction tools, and were finally reported under ACMG guidelines. In our study population, 13 variants were found in the MLH1 gene and 8 in the MSH2 gene. Interestingly, 7 of the 13 MLH1 variants and 3 of the 8 MSH2 variants were novel, whereas the remaining variants were previously reported or available in databases. In addition, some patients with sLS did not have variants in the exons of the MLH1 and MSH2 genes. The variants detected in the MLH1 and MSH2 genes had specific characteristics regarding the number, area of occurrence, and their relationship with demographic and clinicopathologic features.
Overall, our results suggest that analysis of MLH1 and MSH2 genes alone is insufficient in the Iranian population, and more comprehensive tests are recommended for detecting LS.
摘要：
背景：大约5%的结直肠癌（CRC）是遗传性的。林奇综合征（LS），也称为遗传性非息肉病性结直肠癌（HNPCC），是公认的遗传性CRC的最常见形式。尽管伊朗,作为一个发展中国家,CRC的发病率很高，变体的频谱尚未得到彻底研究。
目的：本研究旨在调查疑似林奇综合征（sLS）的伊朗患者MLH1和MSH2基因的致病性和非致病性变异。
结果：在本研究中，从具有sLS和高微卫星不稳定性(MSI-H)的患者收集25个外周血样品。DNA提取后,所有样本均接受聚合酶链反应和Sanger测序,以鉴定MLH1和MSH2基因外显子中的变异.使用预测工具解释识别的变体，并最终在ACMG指南下报告。在我们的研究人群中，在MLH1基因中发现13个变异体，在MSH2基因中发现8个变异体。有趣的是,13个MLH1变体中的7个和8个MSH2变体中的3个是新的，而其余的变异体以前已报告或可在数据库中获得.此外,一些sLS患者在MLH1和MSH2基因的外显子中没有变异.在MLH1和MSH2基因中检测到的变体具有关于数量的特定特征，发生区域,以及它们与人口统计学和临床病理特征的关系。
结论：总体而言，我们的结果表明，在伊朗人口中，仅对MLH1和MSH2基因的分析是不够的，和更全面的测试，建议检测LS。
目的：本研究旨在调查疑似林奇综合征（sLS）的伊朗患者MLH1和MSH2基因的致病性和非致病性变异。
结果：在本研究中，从具有sLS和高微卫星不稳定性(MSI-H)的患者收集25个外周血样品。DNA提取后,所有样本均接受聚合酶链反应和Sanger测序,以鉴定MLH1和MSH2基因外显子中的变异.使用预测工具解释识别的变体，并最终在ACMG指南下报告。在我们的研究人群中，在MLH1基因中发现13个变异体，在MSH2基因中发现8个变异体。有趣的是,13个MLH1变体中的7个和8个MSH2变体中的3个是新的，而其余的变异体以前已报告或可在数据库中获得.此外,一些sLS患者在MLH1和MSH2基因的外显子中没有变异.在MLH1和MSH2基因中检测到的变体具有关于数量的特定特征，发生区域,以及它们与人口统计学和临床病理特征的关系。
结论：总体而言，我们的结果表明，在伊朗人口中，仅对MLH1和MSH2基因的分析是不够的，和更全面的测试，建议检测LS。
