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| 題 名 | HER2 Mutation Profiling in Mucinous Ovarian Carcinoma: Inferences for Enhertu (Trastuzumab Deruxtecan) as a Potential Therapeutic Approach |
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| 作 者 | Shen, Huang-pin; Lee, Ming-yung; Chao, Wan-ru; Sheu, Gwo-tarng; Lee, Yi-ju; Han, Chih-ping; | 書刊名 | Taiwanese Journal of Obstetrics & Gynecology |
| 卷 期 | 64:5 2025.09[民114.09] |
| 頁 次 | 頁802-808 |
| 分類號 | 417.25 |
| 關鍵詞 | HER2 mutations; Mucinous ovarian carcinoma; Tyrosine kinase domain; Next-generation sequencing; Antibody-drug conjugate; |
| 語 文 | 英文(English) |
| DOI | 10.1016/j.tjog.2025.04.013 |
| 英文摘要 | Objective: This study aimed to characterize HER2 mutations in Taiwanese mucinous ovarian carcinoma (mOC) and evaluate the potential of Enhertu (T-DXd) as a targeted therapy for HER2-mutant mOC. Materials and methods: We previously reported a 33.3 % (n = 7/21) HER2 tyrosine kinase domain (TKD) missense mutation rate in mOC using hot-spot PCR and Sanger sequencing. In this study, HER2 mutations were assessed in 18 additional mOC samples using targeted next-generation sequencing (NGS). Data from earlier PCR (n = 21) and current NGS (n = 18) were combined, resulting in all 39 cases. The COSMIC database and PolyPhen-2 (Polymorphism Phenotyping v2) algorithm were used to evaluate the pathogenicity of HER2 mutations identified in the NGS cohort. Results: HER2 mutations were detected in 43.6 % (n = 17/39) of cases. The PCR cohort (n = 21) from the previous 2 studies using PCR and Sanger sequencing identified seven TKD mutations. On the other hand, the NGS cohort (n = 18) from the present study using targeted NGS detected ten non-TKD mutations, with p.P1170A being the most frequent. PolyPhen-2 pathogenicity predictions indicated that p.P1170A and p.R143Q were likely pathogenic. Combining PCR and NGS data enhanced statistical power; however, the study was limited by the insufficient residual specimens from the PCR cohort for NGS reanalysis. Conclusion: Our findings reveal a high prevalence of HER2 mutations in mOC, with distinct profiles in TKD and non-TKD regions. These results support further investigation of Enhertu (T-DXd) as a promising targeted therapy for HER2-mutant mOC. Larger, multi-center studies are needed to validate these findings and explore clinical applications. |
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