High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients

doi:10.1016/j.tjog.2021.09.019

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23563

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23563

Title:	High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
Authors:	Chao, WR;Lee, YJ;Lee, MY;Sheu, GT;Han, CP
Keywords:	Mucinous ovarian carcinoma;BRAF gene;Mutation
Date:	2021
Issue Date:	2022-08-05T09:39:18Z (UTC)
Publisher:	ELSEVIER TAIWAN
ISSN:	1028-4559
Abstract:	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 (R)) 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. (c) 2021 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI:	http://dx.doi.org/10.1016/j.tjog.2021.09.019 https://www.webofscience.com/wos/woscc/full-record/WOS:000722376100019 https://ir.csmu.edu.tw:8080/handle/310902500/23563
Relation:	TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY ,2021,v60,issue 6, P1072-1077
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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