scholarly journals BRAF Gene Amplification Can Promote Acquired Resistance to MEK Inhibitors in Cancer Cells Harboring the BRAF V600E Mutation

2010 ◽  
Vol 3 (149) ◽  
pp. ra84-ra84 ◽  
Author(s):  
R. B. Corcoran ◽  
D. Dias-Santagata ◽  
K. Bergethon ◽  
A. J. Iafrate ◽  
J. Settleman ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Gene Amplification ◽  
Acquired Resistance ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Braf Gene ◽  
Mek Inhibitors

scholarly journals BRAF V600E mutation in hairy cell leukemia: from bench to bedside

Blood ◽  
2016 ◽  
Vol 128 (15) ◽  
pp. 1918-1927 ◽  
Author(s):  
Brunangelo Falini ◽  
Maria Paola Martelli ◽  
Enrico Tiacci
Keyword(s):  
Hairy Cell Leukemia ◽  
Molecular Mechanisms ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Specific Gene ◽  
Hairy Cell ◽  
Braf Inhibitors ◽  
Cell Leukemia ◽  
Genetic Event ◽  
Mek Inhibitors

AbstractHairy cell leukemia (HCL) is a distinct clinicopathological entity whose underlying genetic lesion has remained a mystery for over half a century. The BRAF V600E mutation is now recognized as the causal genetic event of HCL because it is somatic, present in the entire tumor clone, detectable in almost all cases at diagnosis (encompassing the whole disease spectrum), and stable at relapse. BRAF V600E leads to the constitutive activation of the RAF-MEK-extracellular signal-regulated kinase (ERK) signaling pathway which represents the key event in the molecular pathogenesis of HCL. KLF2 and CDNK1B (p27) mutations may cooperate with BRAF V600E in promoting leukemic transformation. Sensitive molecular assays for detecting BRAF V600E allow HCL (highly responsive to purine analogs) to be better distinguished from HCL-like disorders, which are treated differently. In vitro preclinical studies on purified HCL cells proved that BRAF and MEK inhibitors can induce marked dephosphorylation of MEK/ERK, silencing of RAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression profile signature, change of morphology from “hairy” to “smooth,” and eventually apoptosis. The overall response rate of refractory/relapsed HCL patients to the BRAF inhibitor vemurafenib approached 100%, with 35% to 40% complete remissions (CRs). The median relapse free-survival was about 19 months in patients who had achieved CR and 6 months in those who had obtained a partial response. Future therapeutic perspectives include: (1) combining BRAF inhibitors with MEK inhibitors or immunotherapy (anti-CD20 monoclonal antibody) to increase the percentage of CRs and (2) better understanding of the molecular mechanisms underlying resistance of HCL cells to BRAF inhibitors.

Prevalence of BRAF gene mutation in Thai sporadic colorectal cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14051-e14051
Author(s):  
Krittiya Korphaisarn ◽  
Ekkapong Roothumnong ◽  
Akarin Nimmannit ◽  
Chanin Limwongse ◽  
Ananya Manuyakorn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Mutation ◽  
Braf Mutation ◽  
Prognostic Value ◽  
Braf V600e Mutation ◽  
Stage I ◽  
Braf V600e ◽  
Braf Gene ◽  
Primary Tumors ◽  
Caucasian Patients

e14051 Background: The role of BRAF gene mutation has been studied for its association with prognosis of colorectal cancer (CRC). The prevalence was reported 10-15% in Caucasian patients. However, there is no existing data in Thai patients. This study aimed to determine the prevalence of BRAF V600E mutation, association with various clinicopathological features and outcome in Thai sporadic CRC patients. Methods: DNA was extracted from randomly selected formalin-fixed paraffin-embedded tumor blocks of CRC patients with stage I-IV receiving surgery of the primary tumors at Siriraj Hospital between 2006 and 2007. BRAF V600E mutation was performed by two-round allele-specific PCR and analysis using high sensitivity DHPLC. The association between patient characteristics and BRAF status with overall survival (OS) and disease free survival (DFS) were explored by Kaplan-Meier estimation and log-rank test together with Cox’s proportional hazard regression. Results: BRAF V600E mutation was identified in 7 out of 188 patients (3.7%). Four patients were female. There were more likely to found in tumors on the left side (n=4) compared with right side (n=2) and rectum (n=1). All patients with mutation had stage I-III diseases; one with stage I and 3 with stage II and III each. Four had moderately differentiated tumors. Six patients had neither lymphovascular nor perineural invasion. Patients with mutation seemed to have better survival. In multivariate analysis, BRAF mutation did not have major prognostic value regarding DFS or OS. Conclusions: The prevalence of BRAF V600E mutation in Thai sporadic CRC was 3.7% which was lower than what reported in Caucasian patients. Further study with larger number of patients is warranted to determine whether BRAF mutation has significant prognostic value.

scholarly journals Balloon cell melanoma possessed the ability to develop BRAF V600E mutation in cancer cells

2020 ◽  
Author(s):  
Yang‐Yi Chen ◽  
Cheng‐Che E. Lan ◽  
Meng‐Chi Yen ◽  
Shih‐Tsung Cheng
Keyword(s):  
Cancer Cells ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Balloon Cell

scholarly journals Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma

2018 ◽  
pp. 1-5
Author(s):  
Erika Ruiz-Garcia ◽  
Juan A. Matus-Santos ◽  
Jorge Alberto Guadarrama-Orozco ◽  
Miguel Angel Alvarez-Avitia ◽  
Jose Luis Aguilar-Ponce ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Braf Mutation ◽  
Large Scale ◽  
Braf V600e Mutation ◽  
Mexican Population ◽  
Braf V600e ◽  
Braf Gene ◽  
Braf Mutations ◽  
Nodular Melanoma ◽  
Pathologic Features

Purpose The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. Methods Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. Results The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24). Other clinicopathologic features were assessed to correlate with the mutation status. Conclusion This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations.

scholarly journals Mutación BRAF V600E en pacientes con cáncer de tiroides. Fundación Clínica Valle del Lili: una serie de casos

2017 ◽  
Vol 3 (3) ◽  
pp. 45-49
Author(s):  
Guillermo Edinson Guzmán ◽  
Luz Ángela Casas ◽  
Julian David Orrego Celestino ◽  
Juliana Escobar ◽  
Lisa Rodríguez ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Gene Mutation ◽  
Medical Records ◽  
Vascular Invasion ◽  
Lymphatic Invasion ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Nodal Involvement ◽  
Extrathyroid Extension ◽  
Braf Gene

Objetivo: Describir las características clínicas y los hallazgos histopatológicos de los pacientes con diagnóstico de cáncer de tiroides y estudio de la mutación del Gen BRAF V600E.Métodos: Estudio descriptivo, retrospectivo, con información obtenida de las historias clínicas de los pacientes con diagnóstico de cáncer de tiroides atendidos durante 2014 y 2105 en la Fundación Clínica Valle del Lili con estudio para la mutación del gen BRAF V600E.Resultados: De los 344 pacientes con diagnóstico de cáncer de tiroides durante los años 2014 y 2015, se les realizó estudio de la mutación BRAF V600E a 24. La edad promedio fue de 47 años, con predominio en mujeres (87,5%), fueron positivos para la mutación 66% de los pacientes. En relación a las características histopatológicas, el 95,8% de los casos correspondían a cáncer papilar de tiroides, la mayoría de la variedad clásica. Los pacientes con la mutación BRAF V600E tenían mayor extensión extratiroidea, invasión linfática, invasión vascular y compromiso ganglionar, pero no se encontró relación con respecto a tamaño tumoral, multicentralidad, bilateralidad, tiroiditis de Hashimoto o presencia de metástasis.Conclusión: Este es el primer estudio en Colombia, que describe las características clínicas e histopatológicas de los pacientes con cáncer de tiroides en relación a la presencia de la mutacion del Gen BRAF.Abstract Objective: To describe the clinical and histopathological findings of patients diagnosed with thyroid cancer and BRAF V600E gene mutation study. Methods: A descriptive, retrospective study, with information obtained from the medical records of patients diagnosed with thyroid cancer seen during 2014 and 2105 in the Fundacion Clínica Valle del Lili with analysis of the BRAF V600E gene mutation. Results: Of the 344 patients diagnosed with thyroid cancer during the years 2014 and 2015, underwent study of the BRAF V600E to 24. The average age was 47 years, with prevalence in women (87.5%) were positive for mutation 66% of patients. Regarding the histopathologic features, 95.8% of the cases werepapillary thyroid cancer, most classic variety. Patients with BRAF V600E mutation were more extrathyroid extension, lymphatic invasion, vascular invasion and nodal involvement, but no relationship was found with respect to tumor size, multicentrality, bilateralism, Hashimoto’s thyroiditis or presence of metastasis. Conclusion: This is the first study in Colombia, describing the clinical and histopathologic of patients with thyroid cancer in relation to the presence of the BRAF gene mutation characteristics.-

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