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Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test
SIMPLE SUMMARY: Lynch Syndrome (LS) is a hereditary cancer syndrome caused by an autosomal dominant mutation in one of the DNA mismatch repair (MMR) genes. Understanding the clinical traits of endometrial cancer, which is one of the most frequent as well as the earliest diagnosed cancer types of LS-...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316192/ https://www.ncbi.nlm.nih.gov/pubmed/35884469 http://dx.doi.org/10.3390/cancers14143406 |
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author | Kim, Yoo-Na Kim, Min Kyu Lee, Young Joo Lee, Youngeun Sohn, Ji Yeon Lee, Jung-Yun Choi, Min Chul Kim, Migang Jung, Sang Geun Joo, Won Duk Lee, Chan |
author_facet | Kim, Yoo-Na Kim, Min Kyu Lee, Young Joo Lee, Youngeun Sohn, Ji Yeon Lee, Jung-Yun Choi, Min Chul Kim, Migang Jung, Sang Geun Joo, Won Duk Lee, Chan |
author_sort | Kim, Yoo-Na |
collection | PubMed |
description | SIMPLE SUMMARY: Lynch Syndrome (LS) is a hereditary cancer syndrome caused by an autosomal dominant mutation in one of the DNA mismatch repair (MMR) genes. Understanding the clinical traits of endometrial cancer, which is one of the most frequent as well as the earliest diagnosed cancer types of LS-associated cancers, has the potential to offer tailored screening programs and lifesaving interventions. Whereas most large-scale studies of LS-associated endometrial cancers are based on cohorts in Western countries, studies from a predominantly Korean population are relatively few. We conducted a multi-center, retrospective study of patients with endometrial cancer who underwent germline multigene panel testing that included MMR genes. Based on the analysis of 204 patients with endometrial cancer who underwent germline multigene panel testing, we investigated the prevalence of LS and non-LS mutation and the relative contribution of each MMR gene mutation that, in composite, led to the clinical phenotype of LS-associated endometrial cancer patients in a predominantly Korean population. ABSTRACT: We aimed to investigate the prevalence and relative contributions of LS and non-LS mutations in patients with endometrial cancer in Korea. We retrospectively reviewed the medical records of 204 patients diagnosed with endometrial cancer who underwent a germline next generation sequencing multigene panel test covering MLH1, MSH2, MSH6, PMS2, and EPCAM at three tertiary centers. Thirty patients (14.7%) with pathogenic mutations (12 MLH1; 6 MSH2; 10 MSH6; 2 PMS2) and 20 patients (9.8%) with 22 unclassified variants (8 MLH1; 8 MSH2; 2 MSH6; 3 PMS2; 1 EPCAM) were identified. After excluding four close relatives of a proband, the prevalence of LS was 13.0% (26/200). Patients with LS were more likely than those with sporadic cancer to be younger at diagnosis (48 vs. 53 years, p = 0.045) and meet the Amsterdam II criteria (66.7 vs. 3.5%, p < 0.001). Non-endometrioid histology was more prevalent in patients with MSH6 or PMS2 mutations (41.7%) than those with MLH1 or MSH2 mutations (5.6%, p = 0.026). In this pre-selected cohort of endometrial cancer patients who underwent next generation sequencing, the prevalence of LS was 13%, thus supporting the use of gene panel testing for endometrial cancer patients. |
format | Online Article Text |
id | pubmed-9316192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93161922022-07-27 Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test Kim, Yoo-Na Kim, Min Kyu Lee, Young Joo Lee, Youngeun Sohn, Ji Yeon Lee, Jung-Yun Choi, Min Chul Kim, Migang Jung, Sang Geun Joo, Won Duk Lee, Chan Cancers (Basel) Article SIMPLE SUMMARY: Lynch Syndrome (LS) is a hereditary cancer syndrome caused by an autosomal dominant mutation in one of the DNA mismatch repair (MMR) genes. Understanding the clinical traits of endometrial cancer, which is one of the most frequent as well as the earliest diagnosed cancer types of LS-associated cancers, has the potential to offer tailored screening programs and lifesaving interventions. Whereas most large-scale studies of LS-associated endometrial cancers are based on cohorts in Western countries, studies from a predominantly Korean population are relatively few. We conducted a multi-center, retrospective study of patients with endometrial cancer who underwent germline multigene panel testing that included MMR genes. Based on the analysis of 204 patients with endometrial cancer who underwent germline multigene panel testing, we investigated the prevalence of LS and non-LS mutation and the relative contribution of each MMR gene mutation that, in composite, led to the clinical phenotype of LS-associated endometrial cancer patients in a predominantly Korean population. ABSTRACT: We aimed to investigate the prevalence and relative contributions of LS and non-LS mutations in patients with endometrial cancer in Korea. We retrospectively reviewed the medical records of 204 patients diagnosed with endometrial cancer who underwent a germline next generation sequencing multigene panel test covering MLH1, MSH2, MSH6, PMS2, and EPCAM at three tertiary centers. Thirty patients (14.7%) with pathogenic mutations (12 MLH1; 6 MSH2; 10 MSH6; 2 PMS2) and 20 patients (9.8%) with 22 unclassified variants (8 MLH1; 8 MSH2; 2 MSH6; 3 PMS2; 1 EPCAM) were identified. After excluding four close relatives of a proband, the prevalence of LS was 13.0% (26/200). Patients with LS were more likely than those with sporadic cancer to be younger at diagnosis (48 vs. 53 years, p = 0.045) and meet the Amsterdam II criteria (66.7 vs. 3.5%, p < 0.001). Non-endometrioid histology was more prevalent in patients with MSH6 or PMS2 mutations (41.7%) than those with MLH1 or MSH2 mutations (5.6%, p = 0.026). In this pre-selected cohort of endometrial cancer patients who underwent next generation sequencing, the prevalence of LS was 13%, thus supporting the use of gene panel testing for endometrial cancer patients. MDPI 2022-07-13 /pmc/articles/PMC9316192/ /pubmed/35884469 http://dx.doi.org/10.3390/cancers14143406 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Yoo-Na Kim, Min Kyu Lee, Young Joo Lee, Youngeun Sohn, Ji Yeon Lee, Jung-Yun Choi, Min Chul Kim, Migang Jung, Sang Geun Joo, Won Duk Lee, Chan Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test |
title | Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test |
title_full | Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test |
title_fullStr | Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test |
title_full_unstemmed | Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test |
title_short | Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test |
title_sort | identification of lynch syndrome in patients with endometrial cancer based on a germline next generation sequencing multigene panel test |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316192/ https://www.ncbi.nlm.nih.gov/pubmed/35884469 http://dx.doi.org/10.3390/cancers14143406 |
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