BRAF mutational analysis in ovarian tumors: recent perspectives

Wong, Kwong-Kwok; Tsai, Ching‐Chou; Gershenson, David M.

doi:10.2147/plmi.s64383

Cited by 7 publications

(8 citation statements)

References 65 publications

(85 reference statements)

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“…( Previous reports from other countries have shown that MOC has a lower frequency of BRAF mutation (2-20%). [1,2,6] Our data revealed that the BRAF missense mutation rate is relatively up to 80% (n = 16/20) using the FemtoPath BRAF Mutation Screen Kit. This kit is a PCR-based test using proprietary primers which can selectively amplify the somatic mutations in activating segment of the BRAF gene, and suppresses the ampli cation of wild-type BRAF gene in human genomic DNA.…”

Section: Discussionmentioning

confidence: 72%

“…Activating mutations of BRAF can autonomously lead to uncontrolled cellular proliferation and cell survival. The anti-BRAF drugs are successfully used in clinical practice for melanoma and achieve favorable responses for low-grade serous ovarian carcinoma [5,6]. Based on that information, we aimed to explore the BRAF mutation status and evaluate whether it can be a potential therapeutic target for patients with recurrent or advanced stage MOC.…”

Section: Introductionmentioning

confidence: 99%

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

Wan-Ru¹,

Chao²,

Li³

et al. 2020

Preprint

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Background In view of the encouraging clinical evidence of BRAF inhibitors that can treat some 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. Methods DNA was extracted from micro-dissected tissue samples using the QIAamp® DNA FFPE Kit. The 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 subsequent Sanger sequencing method. Additionally, we extended our prior data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. Results Out of the 20 cases tested, 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), dual T599I plus S602F (n = 1). The BRAF missense mutation (S602F) is novel. In addition, the prevalence of BRAF gene mutation is significantly higher than HER2 gene mutation (80% vs. 35%; p = 0.022,) and HER2 gene amplification (80% vs. 35%; p = 0.022), respectively. However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). Discussion Our results showed that BRAF mutation is not uncommon in primary MOC of Taiwanese. When taken together with previous published data, we found that the activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive, but simultaneously independent. However, they may even have a synergistic effect in tumorigenesis. Conclusions The BRAF variant with T599I stands the majority. These findings 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 in MOC. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage MOC patients carrying each class of BRAF mutation.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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

Wan-Ru¹,

Chao²,

Li³

et al. 2020

Preprint

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“…Various studies (such as Wong et al ) using direct Sanger sequencing suggested a better clinical outcome for EOC patients with a BRAF mutation ( 12 ). Preusser et al revealed that patients with invasive carcinomas stained positive for a BRAF V600E monoclonal antibody had a more favorable survival rate ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…BRAF p.V600E, a missense point mutation, is found in approximately 6% of ovarian cancers ( 12 ). Previous studies have shown the BRAF V600E mutation in more than 30% of serous borderline tumors (SBTs), which is associated with low malignant potential (LMP).…”

Section: Introductionmentioning

confidence: 99%

Molecular Status of BRAF Mutation in Epithelial Ovarian Cancer: An Analysis of 57 Cases in the Northeast of Iran

Jafarian,

Jafaripour,

Gharib

et al. 2023

Iran J Pathol

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Background & Objective: Epithelial ovarian cancer (EOC) is the most prevalent type of ovarian cancer. Previous studies have elucidated different pathways for the progression of this malignancy. The mutation in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene, a member of the MAPK/ERK signaling pathway, plays a role in the development of EOC. The current study aimed to determine the frequency of the BRAF V600E mutation in ovarian serous and mucinous tumors, including borderline and carcinoma subtypes. Methods: A total of 57 formalin-fixed paraffin-embedded samples, including serous borderline tumors (SBTs), low-grade serous carcinomas (LGSCs), high-grade serous carcinomas (HGSCs), mucinous borderline tumors (MBTs), and mucinous carcinomas, and 57 normal ovarian tissues were collected. The BRAF V600E mutation was analyzed using polymerase chain reaction (PCR) and sequencing. Results: While 40% of the SBT harbor BRAF mutation, we found no BRAF mutation in the invasive serous carcinoma ( P =0.017). Also, there was only 1 BRAF mutation in MBT and no mutation in mucinous carcinomas. In addition, we found no mutation in the control group. Conclusion: The BRAF mutation is most frequent in borderline tumors but not in invasive serous carcinomas. It seems that 2 different pathways exist for the development of ovarian epithelial neoplasms: one for borderline tumors and the other for high-grade invasive carcinomas. Our study supports this hypothesis. The BRAF mutation is rare in mucinous neoplasms.

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“…In-depth analysis of genetic and histopathological signatures has also led to categorizing OCs into two types, Type I (Low grade) and Type II (High grade). While Type I tumors have a high frequency of KRAS and BRAF mutation, Type II tumors have a high frequency of TP53 mutations [31][32][33][34]. Other biospecimens such as effusions, pap smear fluids, and cervical swabs, are also valuable for understanding OC pathobiology and represent sources of markers that can predict clinical outcomes [35,36].…”

Section: Protein Biomarkers Associated With Ocmentioning

confidence: 99%

Comprehending the Proteomic Landscape of Ovarian Cancer: A Road to the Discovery of Disease Biomarkers

et al. 2021

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Despite recent technological advancements allowing the characterization of cancers at a molecular level along with biomarkers for cancer diagnosis, the management of ovarian cancers (OC) remains challenging. Proteins assume functions encoded by the genome and the complete set of proteins, termed the proteome, reflects the health state. Comprehending the circulatory proteomic profiles for OC subtypes, therefore, has the potential to reveal biomarkers with clinical utility concerning early diagnosis or to predict response to specific therapies. Furthermore, characterization of the proteomic landscape of tumor-derived tissue, cell lines, and PDX models has led to the molecular stratification of patient groups, with implications for personalized therapy and management of drug resistance. Here, we review single and multiple marker panels that have been identified through proteomic investigations of patient sera, effusions, and other biospecimens. We discuss their clinical utility and implementation into clinical practice.

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BRAF mutational analysis in ovarian tumors: recent perspectives

Cited by 7 publications

References 65 publications

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

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

Molecular Status of BRAF Mutation in Epithelial Ovarian Cancer: An Analysis of 57 Cases in the Northeast of Iran

Comprehending the Proteomic Landscape of Ovarian Cancer: A Road to the Discovery of Disease Biomarkers

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