Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea
Abstract Background Therapy-related myeloid neoplasm (T-MN) rarely occurs among cancer survivors, and was characterized by poor prognosis. T-MN has germline predisposition in a considerable proportion. Here, clinical characteristics and germline/somatic variant profiles in T-MN patients were investi...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-023-00458-8 |
| _version_ | 1797864081482317824 |
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| author | Jiwon Yun Hyojin Song Sung-Min Kim Soonok Kim Seok Ryun Kwon Young Eun Lee Dajeong Jeong Jae Hyeon Park Sunghoon Kwon Hongseok Yun Dong Soon Lee |
| author_facet | Jiwon Yun Hyojin Song Sung-Min Kim Soonok Kim Seok Ryun Kwon Young Eun Lee Dajeong Jeong Jae Hyeon Park Sunghoon Kwon Hongseok Yun Dong Soon Lee |
| author_sort | Jiwon Yun |
| collection | DOAJ |
| description | Abstract Background Therapy-related myeloid neoplasm (T-MN) rarely occurs among cancer survivors, and was characterized by poor prognosis. T-MN has germline predisposition in a considerable proportion. Here, clinical characteristics and germline/somatic variant profiles in T-MN patients were investigated, and the findings were compared with those of previous studies. Methods A review of medical records, cytogenetic study, targeted sequencing by next-generation sequencing, and survival analysis were performed on 53 patients with T-MN at a single institution in Korea. Results The patients were relatively younger compared to T-MN patients in other studies. Our T-MN patients showed a high frequency of complex karyotypes, −5/del(5q), and −7/del(7q), which was similar to the Japanese study group but higher than the Australian study group. The most common primary disease was non-Hodgkin lymphoma, followed by breast cancer. The detailed distributions of primary diseases were different across study groups. Seven patients (13.2%) harbored deleterious presumed/potential germline variants in cancer predisposition genes (CPG) such as BRIP1, CEBPA, DDX41, FANCM, NBN, NF1, and RUNX1. In the somatic variant profile, TP53 was the most frequently mutated gene, which was consistent with the previous studies about T-MN. However, the somatic variant frequency in our study group was lower than in other studies. Adverse factors for overall survival were male sex, older age, history of previous radiotherapy, previous longer cytotoxic therapy, and −5/del(5q). Conclusion The findings of our study corroborate important information about T-MN patients. As well as a considerable predisposition to CPG, the clinical characteristics and somatic variant profile showed distinctive patterns. Germline variant testing should be recommended for T-MN patients. If the T-MN patients harbor pathogenic germline variants, the family members for stem cell donation should be screened for carrier status through germline variant testing to avoid donor-derived myeloid neoplasm. For the prediction of the prognosis in T-MN patients, sex, age, past treatment history, and cytogenetic findings can be considered. |
| first_indexed | 2024-04-09T22:45:50Z |
| format | Article |
| id | doaj.art-5a187ce8c60e4562b61c9aecaca68297 |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-09T22:45:50Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-5a187ce8c60e4562b61c9aecaca682972023-03-22T11:50:09ZengBMCHuman Genomics1479-73642023-02-0117111910.1186/s40246-023-00458-8Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in KoreaJiwon Yun0Hyojin Song1Sung-Min Kim2Soonok Kim3Seok Ryun Kwon4Young Eun Lee5Dajeong Jeong6Jae Hyeon Park7Sunghoon Kwon8Hongseok Yun9Dong Soon Lee10Department of Laboratory Medicine, Seoul National University College of MedicineDepartment of Genomic Medicine, Seoul National University HospitalCancer Research Institute, Seoul National University College of MedicineDepartment of Laboratory Medicine, Seoul National University HospitalDepartment of Laboratory Medicine, Seoul National University College of MedicineDepartment of Laboratory Medicine, Seoul National University College of MedicineDepartment of Laboratory Medicine, Seoul National University College of MedicineDepartment of Laboratory Medicine, Seoul National University College of MedicineDepartment of Electrical and Computer Engineering, Seoul National UniversityDepartment of Genomic Medicine, Seoul National University HospitalDepartment of Laboratory Medicine, Seoul National University College of MedicineAbstract Background Therapy-related myeloid neoplasm (T-MN) rarely occurs among cancer survivors, and was characterized by poor prognosis. T-MN has germline predisposition in a considerable proportion. Here, clinical characteristics and germline/somatic variant profiles in T-MN patients were investigated, and the findings were compared with those of previous studies. Methods A review of medical records, cytogenetic study, targeted sequencing by next-generation sequencing, and survival analysis were performed on 53 patients with T-MN at a single institution in Korea. Results The patients were relatively younger compared to T-MN patients in other studies. Our T-MN patients showed a high frequency of complex karyotypes, −5/del(5q), and −7/del(7q), which was similar to the Japanese study group but higher than the Australian study group. The most common primary disease was non-Hodgkin lymphoma, followed by breast cancer. The detailed distributions of primary diseases were different across study groups. Seven patients (13.2%) harbored deleterious presumed/potential germline variants in cancer predisposition genes (CPG) such as BRIP1, CEBPA, DDX41, FANCM, NBN, NF1, and RUNX1. In the somatic variant profile, TP53 was the most frequently mutated gene, which was consistent with the previous studies about T-MN. However, the somatic variant frequency in our study group was lower than in other studies. Adverse factors for overall survival were male sex, older age, history of previous radiotherapy, previous longer cytotoxic therapy, and −5/del(5q). Conclusion The findings of our study corroborate important information about T-MN patients. As well as a considerable predisposition to CPG, the clinical characteristics and somatic variant profile showed distinctive patterns. Germline variant testing should be recommended for T-MN patients. If the T-MN patients harbor pathogenic germline variants, the family members for stem cell donation should be screened for carrier status through germline variant testing to avoid donor-derived myeloid neoplasm. For the prediction of the prognosis in T-MN patients, sex, age, past treatment history, and cytogenetic findings can be considered.https://doi.org/10.1186/s40246-023-00458-8Therapy-related myeloid neoplasmNext-generation sequencingGermline predispositionSomatic mutation |
| spellingShingle | Jiwon Yun Hyojin Song Sung-Min Kim Soonok Kim Seok Ryun Kwon Young Eun Lee Dajeong Jeong Jae Hyeon Park Sunghoon Kwon Hongseok Yun Dong Soon Lee Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea Human Genomics Therapy-related myeloid neoplasm Next-generation sequencing Germline predisposition Somatic mutation |
| title | Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea |
| title_full | Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea |
| title_fullStr | Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea |
| title_full_unstemmed | Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea |
| title_short | Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea |
| title_sort | analysis of clinical and genomic profiles of therapy related myeloid neoplasm in korea |
| topic | Therapy-related myeloid neoplasm Next-generation sequencing Germline predisposition Somatic mutation |
| url | https://doi.org/10.1186/s40246-023-00458-8 |
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