High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
Autor: | Ming-Yung Lee, Gwo-Tarng Sheu, Yi-Ju Lee, Chih-Ping Han, Wan-Ru Chao |
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Rok vydání: | 2021 |
Předmět: |
Adult
Proto-Oncogene Proteins B-raf Mutation rate endocrine system diseases medicine.medical_treatment Taiwan Carcinoma Ovarian Epithelial medicine.disease_cause Targeted therapy Proto-Oncogene Proteins p21(ras) Mucinous ovarian carcinoma medicine Humans Missense mutation skin and connective tissue diseases neoplasms Mitogen-Activated Protein Kinase Kinases Ovarian Neoplasms BRAF gene business.industry MEK inhibitor Melanoma Obstetrics and Gynecology Gynecology and obstetrics medicine.disease Adenocarcinoma Mucinous digestive system diseases enzymes and coenzymes (carbohydrates) Mutation Mutation (genetic algorithm) RG1-991 Cancer research Female KRAS Neoplasm Recurrence Local business V600E |
Zdroj: | Taiwanese Journal of Obstetrics & Gynecology, Vol 60, Iss 6, Pp 1072-1077 (2021) |
ISSN: | 1028-4559 |
Popis: | Objective Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. Materials and methods 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. Results Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). Conclusion Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation. |
Databáze: | OpenAIRE |
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