Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer
Objective: Lynch syndrome (LS) predisposes patients to early onset endometrioid endometrial cancer (EEC). However, little is known about LS-related EEC in the Chinese population. The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese pati...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2020-05-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1622 |
| _version_ | 1828417543944011776 |
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| author | Caixia Ren Yan Liu Yuxiang Wang Yan Tang Yawei Wei Congrong Liu Hongquan Zhang |
| author_facet | Caixia Ren Yan Liu Yuxiang Wang Yan Tang Yawei Wei Congrong Liu Hongquan Zhang |
| author_sort | Caixia Ren |
| collection | DOAJ |
| description | Objective: Lynch syndrome (LS) predisposes patients to early onset endometrioid endometrial cancer (EEC). However, little is known about LS-related EEC in the Chinese population. The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC. Methods: We applied universal immunohistochemistry screening to detect the expression of mismatch repair (MMR) proteins, which was followed by MLH1 methylation analysis to identify suspected LS cases, next-generation sequencing (NGS) to confirm LS, and microsatellite instability (MSI) analysis to verify LS. Results: We collected 211 samples with EEC. Twenty-seven (27/211, 12.8%) EEC cases had a loss of MMR protein expression. After MLH1 methylation analysis, 16 EEC cases were suggested to be associated with LS. Finally, through NGS and MSI analysis, we determined that 10 EEC (10/209, 4.78%) cases were associated with LS. Among those cases, 3 unreported mutations (1 frameshift and 2 nonsense) were identified. MSH6 c.597_597delC, found in 4 patients, is likely to be a founder mutation in China. Conclusions: We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC, by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis. The novel mutations identified in this study expand knowledge of LS. |
| first_indexed | 2024-12-10T14:21:28Z |
| format | Article |
| id | doaj.art-b29f6b4f30254151a5fb17ec5fbcdde5 |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-12-10T14:21:28Z |
| publishDate | 2020-05-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-b29f6b4f30254151a5fb17ec5fbcdde52022-12-22T01:45:10ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412020-05-0117245846710.20892/j.issn.2095-3941.2019.0295Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancerCaixia Ren0Yan Liu1Yuxiang Wang2Yan Tang3Yawei Wei4Congrong Liu5Hongquan Zhang6Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Pathology, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Pathology, Peking University Health Science Center, Beijing 100191, ChinaKey Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Human Anatomy, Basic Medical College of Hebei North University, Zhangjiakou 075000, ChinaDepartment of Pathology, Peking University Health Science Center, Beijing 100191, ChinaKey Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, ChinaObjective: Lynch syndrome (LS) predisposes patients to early onset endometrioid endometrial cancer (EEC). However, little is known about LS-related EEC in the Chinese population. The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC. Methods: We applied universal immunohistochemistry screening to detect the expression of mismatch repair (MMR) proteins, which was followed by MLH1 methylation analysis to identify suspected LS cases, next-generation sequencing (NGS) to confirm LS, and microsatellite instability (MSI) analysis to verify LS. Results: We collected 211 samples with EEC. Twenty-seven (27/211, 12.8%) EEC cases had a loss of MMR protein expression. After MLH1 methylation analysis, 16 EEC cases were suggested to be associated with LS. Finally, through NGS and MSI analysis, we determined that 10 EEC (10/209, 4.78%) cases were associated with LS. Among those cases, 3 unreported mutations (1 frameshift and 2 nonsense) were identified. MSH6 c.597_597delC, found in 4 patients, is likely to be a founder mutation in China. Conclusions: We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC, by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis. The novel mutations identified in this study expand knowledge of LS.http://www.cancerbiomed.org/index.php/cocr/article/view/1622dna mismatch repairendometrial endometrioid cancergermline mutationlynch syndromenext-generation sequencing |
| spellingShingle | Caixia Ren Yan Liu Yuxiang Wang Yan Tang Yawei Wei Congrong Liu Hongquan Zhang Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer Cancer Biology & Medicine dna mismatch repair endometrial endometrioid cancer germline mutation lynch syndrome next-generation sequencing |
| title | Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer |
| title_full | Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer |
| title_fullStr | Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer |
| title_full_unstemmed | Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer |
| title_short | Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer |
| title_sort | identification of novel lynch syndrome mutations in chinese patients with endometriod endometrial cancer |
| topic | dna mismatch repair endometrial endometrioid cancer germline mutation lynch syndrome next-generation sequencing |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1622 |
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