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

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....

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Autores principales:	Wan-Ru Chao, Yi-Ju Lee, Ming-Yung Lee, Gwo-Tarng Sheu, Chih-Ping Han
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Mucinous ovarian carcinoma BRAF gene Mutation Gynecology and obstetrics RG1-991
Acceso en línea:	https://doaj.org/article/66c222cbda7c46129dc0f794551f56e6
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spelling	oai:doaj.org-article:66c222cbda7c46129dc0f794551f56e62021-11-18T04:44:45ZHigh frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients1028-455910.1016/j.tjog.2021.09.019https://doaj.org/article/66c222cbda7c46129dc0f794551f56e62021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S102845592100259Xhttps://doaj.org/toc/1028-4559Objective: 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.Wan-Ru ChaoYi-Ju LeeMing-Yung LeeGwo-Tarng SheuChih-Ping HanElsevierarticleMucinous ovarian carcinomaBRAF geneMutationGynecology and obstetricsRG1-991ENTaiwanese Journal of Obstetrics & Gynecology, Vol 60, Iss 6, Pp 1072-1077 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mucinous ovarian carcinoma BRAF gene Mutation Gynecology and obstetrics RG1-991
spellingShingle	Mucinous ovarian carcinoma BRAF gene Mutation Gynecology and obstetrics RG1-991 Wan-Ru Chao Yi-Ju Lee Ming-Yung Lee Gwo-Tarng Sheu Chih-Ping Han High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
description	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.
format	article
author	Wan-Ru Chao Yi-Ju Lee Ming-Yung Lee Gwo-Tarng Sheu Chih-Ping Han
author_facet	Wan-Ru Chao Yi-Ju Lee Ming-Yung Lee Gwo-Tarng Sheu Chih-Ping Han
author_sort	Wan-Ru Chao
title	High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
title_short	High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
title_full	High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
title_fullStr	High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
title_full_unstemmed	High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients
title_sort	high frequency of braf mutations in primary mucinous ovarian carcinoma of taiwanese patients
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/66c222cbda7c46129dc0f794551f56e6
work_keys_str_mv	AT wanruchao highfrequencyofbrafmutationsinprimarymucinousovariancarcinomaoftaiwanesepatients AT yijulee highfrequencyofbrafmutationsinprimarymucinousovariancarcinomaoftaiwanesepatients AT mingyunglee highfrequencyofbrafmutationsinprimarymucinousovariancarcinomaoftaiwanesepatients AT gwotarngsheu highfrequencyofbrafmutationsinprimarymucinousovariancarcinomaoftaiwanesepatients AT chihpinghan highfrequencyofbrafmutationsinprimarymucinousovariancarcinomaoftaiwanesepatients
_version_	1718425104241655808

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

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