Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndrome

Objective — Lynch syndrome is the most common hereditary cancer syndrome caused by pathogenic variants in the MMR/EPCAM genes. Our goal was to study the germline variants of these genes in the largest sample of patients with Lynch syndrome in Russia. Methods — The study included data on pathogenic...

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Main Authors: Aleksey S. Tsukanov, Aleksey A. Barinov, Vitaly P. Shubin, Anna N. Loginova, Dmitry Yu. Pikunov, Dmitry G. Shakhmatov, Yuri A. Shelygin, Sergey I. Achkasov
Format: Article
Language:English
Published: Limited liability company «Science and Innovations» (Saratov) 2024-09-01
Series:Russian Open Medical Journal
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Online Access:https://romj.org/node/569
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author Aleksey S. Tsukanov
Aleksey A. Barinov
Vitaly P. Shubin
Anna N. Loginova
Dmitry Yu. Pikunov
Dmitry G. Shakhmatov
Yuri A. Shelygin
Sergey I. Achkasov
author_facet Aleksey S. Tsukanov
Aleksey A. Barinov
Vitaly P. Shubin
Anna N. Loginova
Dmitry Yu. Pikunov
Dmitry G. Shakhmatov
Yuri A. Shelygin
Sergey I. Achkasov
author_sort Aleksey S. Tsukanov
collection DOAJ
description Objective — Lynch syndrome is the most common hereditary cancer syndrome caused by pathogenic variants in the MMR/EPCAM genes. Our goal was to study the germline variants of these genes in the largest sample of patients with Lynch syndrome in Russia. Methods — The study included data on pathogenic and likely pathogenic variants in the MMR/EPCAM genes collected from the local Registry of Hereditary Colorectal Cancer of Ryzhikh National Medical Research Centre for Coloproctology (RNMRCC). We analyzed all available data on 141 probands with Lynch syndrome: 78 men and 63 women aged 21 to 80 years treated at RNMRCC from 2012 through 2023. Results — The numbers of pathogenic and likely pathogenic variants detected in the key genes were as follows MLH1 (69 probands), MSH2 (57), MSH6 (10), EPCAM (3), PMS2 (1), and PMS1 (1). Of the 141 germline variants, 17 (12.1%) were detected for the first time: MLH1 (8 probands) MSH2 (8), and MSH6 (1). Thirteen (9.2%) of the detected variants were associated with large deletions/duplications. The most frequent pathogenic variants in the MLH1 gene were c.1852_1854del (9 probands), c.350C>T (4), and c.1459C>T (3). The most frequent pathogenic variants in the MSH2 gene were c.942+3A>T (9 probands) and c.1288A>T (3). Conclusion — Our results allowed establishing the frequency and spectrum of different types of germline variants in the MMR/EPCAM genes, which helped optimize the algorithm for selecting and diagnosing Russian patients with Lynch syndrome.
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spelling doaj-art-4fda5d1dd3854f8488a3340107f09e1f2025-08-20T02:03:07ZengLimited liability company «Science and Innovations» (Saratov)Russian Open Medical Journal2304-34152024-09-01133e030810.15275/rusomj.2024.0308Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndromeAleksey S. TsukanovAleksey A. BarinovVitaly P. ShubinAnna N. LoginovaDmitry Yu. PikunovDmitry G. ShakhmatovYuri A. ShelyginSergey I. AchkasovObjective — Lynch syndrome is the most common hereditary cancer syndrome caused by pathogenic variants in the MMR/EPCAM genes. Our goal was to study the germline variants of these genes in the largest sample of patients with Lynch syndrome in Russia. Methods — The study included data on pathogenic and likely pathogenic variants in the MMR/EPCAM genes collected from the local Registry of Hereditary Colorectal Cancer of Ryzhikh National Medical Research Centre for Coloproctology (RNMRCC). We analyzed all available data on 141 probands with Lynch syndrome: 78 men and 63 women aged 21 to 80 years treated at RNMRCC from 2012 through 2023. Results — The numbers of pathogenic and likely pathogenic variants detected in the key genes were as follows MLH1 (69 probands), MSH2 (57), MSH6 (10), EPCAM (3), PMS2 (1), and PMS1 (1). Of the 141 germline variants, 17 (12.1%) were detected for the first time: MLH1 (8 probands) MSH2 (8), and MSH6 (1). Thirteen (9.2%) of the detected variants were associated with large deletions/duplications. The most frequent pathogenic variants in the MLH1 gene were c.1852_1854del (9 probands), c.350C>T (4), and c.1459C>T (3). The most frequent pathogenic variants in the MSH2 gene were c.942+3A>T (9 probands) and c.1288A>T (3). Conclusion — Our results allowed establishing the frequency and spectrum of different types of germline variants in the MMR/EPCAM genes, which helped optimize the algorithm for selecting and diagnosing Russian patients with Lynch syndrome.https://romj.org/node/569lynch syndromecolorectal cancermicrosatellite instabilitymmr/epcam genes
spellingShingle Aleksey S. Tsukanov
Aleksey A. Barinov
Vitaly P. Shubin
Anna N. Loginova
Dmitry Yu. Pikunov
Dmitry G. Shakhmatov
Yuri A. Shelygin
Sergey I. Achkasov
Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndrome
Russian Open Medical Journal
lynch syndrome
colorectal cancer
microsatellite instability
mmr/epcam genes
title Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndrome
title_full Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndrome
title_fullStr Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndrome
title_full_unstemmed Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndrome
title_short Germline variants of the MMR/EPCAM genes in Russian patients with Lynch syndrome
title_sort germline variants of the mmr epcam genes in russian patients with lynch syndrome
topic lynch syndrome
colorectal cancer
microsatellite instability
mmr/epcam genes
url https://romj.org/node/569
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