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Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary

INTRODUCTION: Lynch syndrome is an autosomal dominant disorder, most frequent leading to colon cancer. Identification of patients with Lynch syndrome and screening of their family members are available prevention approach that can significantly decrease mortality. Unfortunately, routine screening st...

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Autores principales: Kóder, Gergely, Olasz, Judit, Tanyi, Janos L., George, Erin, Tóth, László, Antal-Szalmás, Péter, Nagy, Béla, Bubán, Tamás, András, Csilla, Urbancsek, Hilda, Laczik, Miklós, Csuka, Orsolya, Damjanovich, László, Tanyi, Miklós
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399673/
https://www.ncbi.nlm.nih.gov/pubmed/31939059
http://dx.doi.org/10.1007/s12029-020-00359-2
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author Kóder, Gergely
Olasz, Judit
Tanyi, Janos L.
George, Erin
Tóth, László
Antal-Szalmás, Péter
Nagy, Béla
Bubán, Tamás
András, Csilla
Urbancsek, Hilda
Laczik, Miklós
Csuka, Orsolya
Damjanovich, László
Tanyi, Miklós
author_facet Kóder, Gergely
Olasz, Judit
Tanyi, Janos L.
George, Erin
Tóth, László
Antal-Szalmás, Péter
Nagy, Béla
Bubán, Tamás
András, Csilla
Urbancsek, Hilda
Laczik, Miklós
Csuka, Orsolya
Damjanovich, László
Tanyi, Miklós
author_sort Kóder, Gergely
collection PubMed
description INTRODUCTION: Lynch syndrome is an autosomal dominant disorder, most frequent leading to colon cancer. Identification of patients with Lynch syndrome and screening of their family members are available prevention approach that can significantly decrease mortality. Unfortunately, routine screening still does not belong to standard of care in Hungary. In this study, we performed a comprehensive screening in order to identify patients with mismatch repair (MMR) mutation between the years of 2011 and 2014. Identified mutations were compared with those already published in the international databases. PATIENTS AND METHODS: Patients who underwent treatment for colorectal cancer at the Surgical Institute of the University of Debrecen were screened using the modified Amsterdam and Bethesda Criteria. Immunohistochemistry and microsatellite analyses were performed in order to identify possible mutation carrier cases. Suspicious cases underwent DNA sequencing to detect mutations in the mismatch repair genes (hMLH1, hMSH2). RESULTS: All together 760 colorectal cancer patients were screened. A total of 28 patients were identified as possible MMR mutation carrier and underwent further genetic evaluation. Pathogenic sequence variants of the MMR gene were found in 5 patients. Hypermethylation of the promoter region of the hMLH1 gene was identified in 2 patients. Two out of the 5 pathogenic sequence variants of the MMR gene were first identified by our group while other 2 mutations were previously published as possible founder mutations. CONCLUSION: Identification of families with Lynch syndrome, while challenging because of variable phenotypes at diagnosis, is feasible with available molecular biological technologies and crucial to reduce mortality caused by this syndrome.
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spelling pubmed-73996732020-08-13 Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary Kóder, Gergely Olasz, Judit Tanyi, Janos L. George, Erin Tóth, László Antal-Szalmás, Péter Nagy, Béla Bubán, Tamás András, Csilla Urbancsek, Hilda Laczik, Miklós Csuka, Orsolya Damjanovich, László Tanyi, Miklós J Gastrointest Cancer Original Research INTRODUCTION: Lynch syndrome is an autosomal dominant disorder, most frequent leading to colon cancer. Identification of patients with Lynch syndrome and screening of their family members are available prevention approach that can significantly decrease mortality. Unfortunately, routine screening still does not belong to standard of care in Hungary. In this study, we performed a comprehensive screening in order to identify patients with mismatch repair (MMR) mutation between the years of 2011 and 2014. Identified mutations were compared with those already published in the international databases. PATIENTS AND METHODS: Patients who underwent treatment for colorectal cancer at the Surgical Institute of the University of Debrecen were screened using the modified Amsterdam and Bethesda Criteria. Immunohistochemistry and microsatellite analyses were performed in order to identify possible mutation carrier cases. Suspicious cases underwent DNA sequencing to detect mutations in the mismatch repair genes (hMLH1, hMSH2). RESULTS: All together 760 colorectal cancer patients were screened. A total of 28 patients were identified as possible MMR mutation carrier and underwent further genetic evaluation. Pathogenic sequence variants of the MMR gene were found in 5 patients. Hypermethylation of the promoter region of the hMLH1 gene was identified in 2 patients. Two out of the 5 pathogenic sequence variants of the MMR gene were first identified by our group while other 2 mutations were previously published as possible founder mutations. CONCLUSION: Identification of families with Lynch syndrome, while challenging because of variable phenotypes at diagnosis, is feasible with available molecular biological technologies and crucial to reduce mortality caused by this syndrome. Springer US 2020-01-14 2020 /pmc/articles/PMC7399673/ /pubmed/31939059 http://dx.doi.org/10.1007/s12029-020-00359-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Research
Kóder, Gergely
Olasz, Judit
Tanyi, Janos L.
George, Erin
Tóth, László
Antal-Szalmás, Péter
Nagy, Béla
Bubán, Tamás
András, Csilla
Urbancsek, Hilda
Laczik, Miklós
Csuka, Orsolya
Damjanovich, László
Tanyi, Miklós
Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
title Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
title_full Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
title_fullStr Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
title_full_unstemmed Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
title_short Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary
title_sort identification of novel pathogenic sequence variants of the mismatch repair genes during screening for lynch syndrome in a single centre of eastern hungary
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399673/
https://www.ncbi.nlm.nih.gov/pubmed/31939059
http://dx.doi.org/10.1007/s12029-020-00359-2
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