Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report
Introduction: Lynch syndrome is caused by a germline mutation in mismatch repair (MMR) genes, leading to the loss of expression of MMR heterodimers, either MLH1/PMS2 or MSH2/MSH6, or isolated loss of PMS2 or MSH6. Concurrent loss of both heterodimers is uncommon, and patients carrying pathogenic var...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Gynecologic Oncology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352578924000602 |
| _version_ | 1797232859218444288 |
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| author | Yi-Ching Huang Peng-Chan Lin Pei-Ying Wu Nai-Syuan Chen Meng-Ru Shen Yu-Min Yeh Ya-Min Cheng |
| author_facet | Yi-Ching Huang Peng-Chan Lin Pei-Ying Wu Nai-Syuan Chen Meng-Ru Shen Yu-Min Yeh Ya-Min Cheng |
| author_sort | Yi-Ching Huang |
| collection | DOAJ |
| description | Introduction: Lynch syndrome is caused by a germline mutation in mismatch repair (MMR) genes, leading to the loss of expression of MMR heterodimers, either MLH1/PMS2 or MSH2/MSH6, or isolated loss of PMS2 or MSH6. Concurrent loss of both heterodimers is uncommon, and patients carrying pathogenic variants affecting different MMR genes are rare, leading to the lack of cancer screening recommendation for these patients.Case presentation:Here, we reported a female with a family history of Lynch syndrome with MLH1 c.676C > T mutation. She developed endometrial cancer at 37 years old, with loss of MLH1/PMS2 expression. Immunohistochemical staining on tumor samples incidentally detected the additional loss of MSH6 expression. Whole exome sequencing on genomic DNA from peripheral blood revealed MSH6 c.2731C > T mutation, which was confirmed to be inherited from her mother, who had an early-onset ascending colon cancer without cancer family history. Conclusion: This is a rare case of the Lynch syndrome harboring germline mutations simultaneously in two different MMR genes inherited from two families with Lynch syndrome. The diagnosis of endometrial cancer at the age less than 40 years is uncommon for Lynch syndrome-related endometrial cancer. This suggests an earlier cancer screening for patients carrying two MMR mutations. |
| first_indexed | 2024-04-24T16:06:58Z |
| format | Article |
| id | doaj.art-e2818d5f063a4540be45c05cb287877c |
| institution | Directory Open Access Journal |
| issn | 2352-5789 |
| language | English |
| last_indexed | 2024-04-24T16:06:58Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gynecologic Oncology Reports |
| spelling | doaj.art-e2818d5f063a4540be45c05cb287877c2024-04-01T04:04:21ZengElsevierGynecologic Oncology Reports2352-57892024-06-0153101381Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case reportYi-Ching Huang0Peng-Chan Lin1Pei-Ying Wu2Nai-Syuan Chen3Meng-Ru Shen4Yu-Min Yeh5Ya-Min Cheng6Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Genomic Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, TaiwanDepartment of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, TaiwanDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Corresponding authors at: Department of Oncology, National Cheng Kung University Hospital, Tainan 704, Taiwan, No.138, Sheng-Li Road, Tainan, Taiwan, Superintendent, Kuo General Hospital, Tainan, Taiwan, No.22, Sec 2, Minsheng Road, Tainan, Taiwan.Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Taiwan; Superintendent, Kuo General Hospital, Tainan, Taiwan; Corresponding authors at: Department of Oncology, National Cheng Kung University Hospital, Tainan 704, Taiwan, No.138, Sheng-Li Road, Tainan, Taiwan, Superintendent, Kuo General Hospital, Tainan, Taiwan, No.22, Sec 2, Minsheng Road, Tainan, Taiwan.Introduction: Lynch syndrome is caused by a germline mutation in mismatch repair (MMR) genes, leading to the loss of expression of MMR heterodimers, either MLH1/PMS2 or MSH2/MSH6, or isolated loss of PMS2 or MSH6. Concurrent loss of both heterodimers is uncommon, and patients carrying pathogenic variants affecting different MMR genes are rare, leading to the lack of cancer screening recommendation for these patients.Case presentation:Here, we reported a female with a family history of Lynch syndrome with MLH1 c.676C > T mutation. She developed endometrial cancer at 37 years old, with loss of MLH1/PMS2 expression. Immunohistochemical staining on tumor samples incidentally detected the additional loss of MSH6 expression. Whole exome sequencing on genomic DNA from peripheral blood revealed MSH6 c.2731C > T mutation, which was confirmed to be inherited from her mother, who had an early-onset ascending colon cancer without cancer family history. Conclusion: This is a rare case of the Lynch syndrome harboring germline mutations simultaneously in two different MMR genes inherited from two families with Lynch syndrome. The diagnosis of endometrial cancer at the age less than 40 years is uncommon for Lynch syndrome-related endometrial cancer. This suggests an earlier cancer screening for patients carrying two MMR mutations.http://www.sciencedirect.com/science/article/pii/S2352578924000602Lynch syndromeEndometrial cancerColorectal cancerDNA mismatch repairMLH1MSH6 |
| spellingShingle | Yi-Ching Huang Peng-Chan Lin Pei-Ying Wu Nai-Syuan Chen Meng-Ru Shen Yu-Min Yeh Ya-Min Cheng Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report Gynecologic Oncology Reports Lynch syndrome Endometrial cancer Colorectal cancer DNA mismatch repair MLH1 MSH6 |
| title | Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report |
| title_full | Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report |
| title_fullStr | Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report |
| title_full_unstemmed | Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report |
| title_short | Germline MLH1 and MSH6 mutations from two Lynch syndrome families identified in a patient with early-onset of endometrial cancer: A case report |
| title_sort | germline mlh1 and msh6 mutations from two lynch syndrome families identified in a patient with early onset of endometrial cancer a case report |
| topic | Lynch syndrome Endometrial cancer Colorectal cancer DNA mismatch repair MLH1 MSH6 |
| url | http://www.sciencedirect.com/science/article/pii/S2352578924000602 |
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