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Rare single‐nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome
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  • Seyed Mohsen Mirabdolhosseini,
  • Mohammad Yaghoob Taleghani,
  • Leili Rejali,
  • hossein sadeghi,
  • Nayeralsadat Fatemi,
  • Mehdi Tavallaei ,
  • Amin Famil Meyari,
  • Narges Saeidi ,
  • Amir Sadeghi ,
  • Hamid Asadzadeh Aghdaei,
  • Mohammad Reza Zali,
  • Ehsan Nazemalhosseini Mojarad
Seyed Mohsen Mirabdolhosseini
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Mohammad Yaghoob Taleghani
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Leili Rejali
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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hossein sadeghi
genomic research center, shahid beheshti university Shahid Beheshti University of Medical Sciences
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Nayeralsadat Fatemi
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Mehdi Tavallaei
Department of Colorectal Surgery, Medical Science of Shahid Beheshti University, Tehran, Iran
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Amin Famil Meyari
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Narges Saeidi
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Amir Sadeghi
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Hamid Asadzadeh Aghdaei
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Mohammad Reza Zali
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases
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Ehsan Nazemalhosseini Mojarad
Shahid Beheshti University of Medical Sciences Research Institute for Gastroenterology and Liver Diseases

Corresponding Author:[email protected]

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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, a developing country, has a high incidence of CRC, the spectrum of mutations has yet to be thoroughly investigated. Therefore, 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 (PCR) and Sanger sequencing to identify the variants in the exons of MLH1 and MSH2 genes. The identified variants were interpreted using prediction tools, including SIFT, CADD, PolyPhen, PROVEAN, REVEL, MetaLR, and Mutational Assessor. 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. We identified two novel pathogenic/likely pathogenic variants in these two genes. 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.
18 May 2023Submitted to Cancer Reports
01 Jun 2023Submission Checks Completed
01 Jun 2023Assigned to Editor
05 Jun 2023Review(s) Completed, Editorial Evaluation Pending
06 Jun 2023Reviewer(s) Assigned
06 Jul 2023Editorial Decision: Revise Major
12 Aug 20231st Revision Received
25 Aug 2023Submission Checks Completed
25 Aug 2023Assigned to Editor
25 Aug 2023Review(s) Completed, Editorial Evaluation Pending
26 Aug 2023Reviewer(s) Assigned
14 Sep 2023Editorial Decision: Revise Minor
27 Sep 20232nd Revision Received
29 Sep 2023Submission Checks Completed
29 Sep 2023Assigned to Editor
29 Sep 2023Review(s) Completed, Editorial Evaluation Pending
06 Oct 2023Reviewer(s) Assigned
17 Oct 2023Editorial Decision: Accept