Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome
Abstract Background 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 spect...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.1930 |
| _version_ | 1797344836218519552 |
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| author | Seyed Mohsen Mirabdolhosseini Mohammad Yaghoob Taleghani Leili Rejali Hossein Sadeghi Nayeralsadat Fatemi Mehdi Tavallaei Amin Famil Meyari Narges Saeidi Pardis Ketabi Moghadam Amir Sadeghi Hamid Asadzadeh Aghdaei Mohammad Reza Zali Ehsan Nazemalhosseini Mojarad |
| author_facet | Seyed Mohsen Mirabdolhosseini Mohammad Yaghoob Taleghani Leili Rejali Hossein Sadeghi Nayeralsadat Fatemi Mehdi Tavallaei Amin Famil Meyari Narges Saeidi Pardis Ketabi Moghadam Amir Sadeghi Hamid Asadzadeh Aghdaei Mohammad Reza Zali Ehsan Nazemalhosseini Mojarad |
| author_sort | Seyed Mohsen Mirabdolhosseini |
| collection | DOAJ |
| description | Abstract Background 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. Aims This study aimed to investigate pathogenic and non‐pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS). Methods and results 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. Conclusion 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. |
| first_indexed | 2024-03-08T11:08:39Z |
| format | Article |
| id | doaj.art-a454974b56704bf9a1743d83cb433cff |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-03-08T11:08:39Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
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| series | Cancer Reports |
| spelling | doaj.art-a454974b56704bf9a1743d83cb433cff2024-01-26T14:25:02ZengWileyCancer Reports2573-83482024-01-0171n/an/a10.1002/cnr2.1930Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndromeSeyed Mohsen Mirabdolhosseini0Mohammad Yaghoob Taleghani1Leili Rejali2Hossein Sadeghi3Nayeralsadat Fatemi4Mehdi Tavallaei5Amin Famil Meyari6Narges Saeidi7Pardis Ketabi Moghadam8Amir Sadeghi9Hamid Asadzadeh Aghdaei10Mohammad Reza Zali11Ehsan Nazemalhosseini Mojarad12Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranGenomic Research Center Shahid Beheshti University of Medical Sciences Tehran IranBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Colorectal Surgery Medical Science of Shahid Beheshti University Tehran IranBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranGastroenterology and Liver Diseases Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranGastroenterology and Liver Diseases Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranGastroenterology and Liver Diseases Research Center Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences Tehran IranAbstract Background 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. Aims This study aimed to investigate pathogenic and non‐pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS). Methods and results 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. Conclusion 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.https://doi.org/10.1002/cnr2.1930non‐pathogenic variantsLynch syndromeMLH1MSH2pathogenic variants |
| spellingShingle | Seyed Mohsen Mirabdolhosseini Mohammad Yaghoob Taleghani Leili Rejali Hossein Sadeghi Nayeralsadat Fatemi Mehdi Tavallaei Amin Famil Meyari Narges Saeidi Pardis Ketabi Moghadam Amir Sadeghi Hamid Asadzadeh Aghdaei Mohammad Reza Zali Ehsan Nazemalhosseini Mojarad Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome Cancer Reports non‐pathogenic variants Lynch syndrome MLH1 MSH2 pathogenic variants |
| title | Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome |
| title_full | Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome |
| title_fullStr | Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome |
| title_full_unstemmed | Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome |
| title_short | Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome |
| title_sort | rare single nucleotide variants of mlh1 and msh2 genes in patients with lynch syndrome |
| topic | non‐pathogenic variants Lynch syndrome MLH1 MSH2 pathogenic variants |
| url | https://doi.org/10.1002/cnr2.1930 |
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