BRAF Mutations in Low-Grade Serous Ovarian Cancer and Response to BRAF Inhibition

Purpose Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma–mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic BRAF. However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with BRAF-mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of BRAF-mutated LGSC and described the response to treatment with BRAF inhibitors. Patients and Methods Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic BRAF V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. Results Among patients with LGSC, nine (13.8%) of 65 had a somatic BRAF mutation. Of the nine patients with BRAF mutation–positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with BRAF V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. Conclusion BRAF mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit.

Download Full-text

Cutaneous Side Effects of BRAF Inhibitors in Advanced Melanoma: Review of the Literature

Dermatology Research and Practice ◽

10.1155/2016/5361569 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 27

Author(s):

Bilgen Gençler ◽

Müzeyyen Gönül

Keyword(s):

Side Effects ◽

Metastatic Melanoma ◽

Mapk Pathway ◽

Case Reports ◽

Mitogen Activated Protein Kinase ◽

Braf V600e ◽

Braf Inhibitors ◽

Braf Mutations ◽

Cutaneous Side Effects ◽

Downstream Signaling

The incidence of melanoma has recently been increasing. BRAF mutations have been found in 40–60% of melanomas. The increased activity of BRAF V600E leads to the activation of downstream signaling through the mitogen-activated protein kinase (MAPK) pathway, which plays a key role as a regulator of cell growth, differentiation, and survival. The use of BRAF inhibitors in metastatic melanoma with BRAF mutation ensures clinical improvement of the disease. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the Food and Drug Administration (FDA). Both drugs are well tolerated and successfully used in clinical practice. However, some adverse reactions have been reported in patients in the course of treatment. Cutaneous side effects are the most common adverse events among them with a broad spectrum. Both the case reports and several original clinical trials reported cutaneous reactions during the treatment with BRAF inhibitors. In this review, the common cutaneous side effects of BRAF inhibitors in the treatment of metastatic melanoma with BRAF V600E mutation were reviewed.

Download Full-text

Polymorphous Low-Grade Neuroepithelial Tumor of the Young (PLNTY): Molecular Profiling Confirms Frequent MAPK Pathway Activation

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlab075 ◽

2021 ◽

Author(s):

Cristiane M Ida ◽

Derek R Johnson ◽

Asha A Nair ◽

Jaime Davila ◽

Thomas M Kollmeyer ◽

...

Keyword(s):

Copy Number ◽

Mapk Pathway ◽

Braf V600e Mutation ◽

Mitogen Activated Protein Kinase ◽

Braf V600e ◽

Low Grade ◽

Pathway Activation ◽

Mitogen Activated Protein ◽

Copy Number Changes ◽

Cd34 Expression

Abstract Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5–52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.

Download Full-text

RARE-32. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG (PLNTY): GENETIC ANALYSIS CONFIRMS FREQUENT MAPK PATHWAY ACTIVATION

Neuro-Oncology ◽

10.1093/neuonc/noz175.955 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi228-vi228

Author(s):

Cristiane Ida ◽

Derek Johnson ◽

Thomas Kollmeyer ◽

DongKun Kim ◽

Timothy Kaufmann ◽

...

Keyword(s):

Pilocytic Astrocytoma ◽

Mapk Pathway ◽

Braf V600e Mutation ◽

Braf V600e ◽

Chromosome 17 ◽

Chromosomal Microarray ◽

Low Grade ◽

Fusion Event ◽

Dna And Rna ◽

Pathway Activation

Abstract Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and genetic MAPK pathway activation through alterations such as BRAF V600E mutation, and FGFR2-KIAA1598/CTNNA3 and FGFR3-TACC3 fusions. We report the molecular profiling of PLNTY in 9 patients, 7 female: 2 male, median age at diagnosis of 16 years (range, 5–34). All tumors were supratentorial with diagnostic morphological features of PLNTY including oligodendroglioma-like areas and strong diffuse CD34 immunostaining. Four (of 9; 44%) tumors were positive for BRAF V600E immunostain, indicating the presence of a BRAF V600E mutation. The 6 cases evaluated for IDH status were negative by IDH1-R132H immunostain (n=5; 3 BRAF V600E-negative and 2 BRAF V600E-positive) or by NGS (n=1; BRAF V600E-negative). Oncoscan chromosomal microarray performed in 5 BRAF V600E-negative tumors showed recurrent copy number changes including gain of whole chromosomes 5, 7, 8, 9, 12, 18, 19, 20, 21 and X, and loss of chromosomes 1, 2, 10q, 13, 22 and Xq. The 10q losses (n=2) were highly suggestive of an FGFR2-KIAA1598 and of a potentially novel FGFR2 underlying fusion event in one case each. Custom targeted neuro-oncology DNA and RNA NGS panel performed in 2 cases revealed a fusion similar to fusions previously reported in pilocytic astrocytoma: one with a KIAA1549-BRAF (exon 15-exon 9) fusion associated with a 7q34 ~785 kilobase deletion rather than the characteristic ~2 megabase duplication seen in pilocytic astrocytoma, and another with a QKI-NTRK2 (exon 6-exon 15) fusion associated with a 9q21 ~191 kilobase duplication disrupting NTRK2. The KIAA1549-BRAF fusion-positive case also had a TP53 mutation with loss of whole chromosome 17, suggesting TP53 complete inactivation. This study confirms that PLNTY is a low-grade neuroepithelial tumor with frequent MAPK pathway activation and expands the spectrum of MAPK activating alterations observed in PLNTY.

Download Full-text

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

Journal of Global Oncology ◽

10.1200/jgo.2016.008912 ◽

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.

Download Full-text

Association of BRAF V600E Mutation with Poor Clinicopathological Outcomes in 500 Consecutive Cases of Papillary Thyroid Carcinoma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-1179 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4085-4090 ◽

Cited By ~ 263

Author(s):

Cristiana Lupi ◽

Riccardo Giannini ◽

Clara Ugolini ◽

Agnese Proietti ◽

Piero Berti ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Braf Mutation ◽

Braf V600e Mutation ◽

Braf V600e ◽

Clinicopathological Parameters ◽

Papillary Thyroid ◽

Braf Mutations ◽

Tumor Capsule ◽

Extrathyroidal Invasion

Abstract Context: Because very few studies have examined the correlation between BRAF mutations and clinicopathological features of papillary thyroid carcinoma (PTC), we analyzed here a large and homogeneous cohort of patients with PTC for the presence of the BRAF mutation. Objective: We examined BRAF mutations in a consecutive series of 500 PTC patients who underwent surgery in the Department of Surgery of the University of Pisa, and we correlated the presence of the mutation with clinicopathological parameters of the patients: age, gender, tumor size, presence of tumor capsule, extrathyroidal invasion, multicentricity, presence of node metastases, and tumor class. Design: BRAF (exon 15) mutation was examined by PCR-single strand conformational polymorphism followed by DNA sequencing in laser-capture microdissected tissue samples. Results: In this study, BRAF mutation was found in 219 of 500 cases (43.8%). In particular, we found the most common BRAF V600E mutation in 214 cases (42.8%), BRAF K601E mutation in three cases (0.6%), BRAF VK600–1E (0.2%) in one case, whereas in one case we found a new 14-bp deletion with concomitant 2-bp insertion, VKSR600–3del and T599I, respectively. BRAF V600E was associated with extrathyroidal invasion (P < 0.0001), multicentricity (P = 0.0026), presence of nodal metastases (P = 0.0009), class III vs. classes I and II (P < 0.00000006), and absence of tumor capsule (P < 0.0001), in particular in follicular- and micro-PTC variants. By multivariate analysis, the absence of tumor capsule remained the only parameter associated (P = 0.0005) with BRAF V600E mutation. Conclusions: Our data suggest that BRAF V600E mutation is associated with high-risk PTC and in particular in follicular variant with invasive tumor growth.

Download Full-text

BRAF V600E Targetable Mutation in Relapsed/Refractory Multiple Myeloma (R/R MM) Patients: A High Incidence in R/R MM Detected Using Cell Sorting Screening

Blood ◽

10.1182/blood.v128.22.5638.5638 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5638-5638

Author(s):

Alina Danu ◽

Sophie Cotteret ◽

Ludovic Lacroix ◽

Véronique Saada ◽

Véronique Vergé ◽

...

Keyword(s):

Bone Marrow ◽

Board Of Directors ◽

Cell Sorting ◽

Braf Mutation ◽

Research Funding ◽

Braf V600e Mutation ◽

Braf V600e ◽

Newly Diagnosed ◽

Braf Mutations ◽

Advisory Committees

Abstract Background: The oncogenic BRAF V600E mutation activates the MAPK signaling pathway resulting in cell growth and survival of tumor cells carrying the mutation. Targeting BRAF has shown its efficacy in metastatic melanomas. BRAF V600E mutation has been described in multiple myeloma (MM), with an incidence of 4-10% in previous reports. We report here the incidence of BRAF mutations in a series of MM patients treated at our center. Methods: From February 2012 to March 2016, 94 MM patients were tested for BRAF mutations. Eighty-one samples came from patients with relapsed/refractory MM (R/R MM) and 13 samples from newly diagnosed patients. Eighty-eight samples were collected from bone marrow aspirates, 3 from extramedullary plasmacytoma biopsies, 1 from pleural effusion, and 2 from peripheral blood. Targeted sequencing for BRAF mutations using Sanger direct sequencing or targeted next generation sequencing were performed on all samples after CD138 cell (after 2015). In addition, NGS was performed for 2 patients. From 2012 to 2015, we used material obtained from scraping bone marrow smears with > 20% plasma cells. Since 2015, we began using immunomagnetic cell-sorting based on the CD138 cell surface marker (Stem Cells®). Results: BRAF mutations were detected in 8 samples out of the 84 that could have been screened (9.5%). When considering only the relapsed/refractory population, the incidence of BRAF mutations was 10.8%. One sample had the inactivating D594N BRAF mutation and the other 7 had the V600E BRAF mutation. The 8 mutated patients had relapsed/refractory MM at the time of analysis. Of note, 5 out of the 8 mutated patients (62.5%) had an IgA MM. Seventy-six samples had no BRAF mutation detectable. Ten samples were not tested because of the small percentage of MM cells on the bone marrow smears. The failure rate was 16% with the scraping technique and 3.4% with the sorting cell technique. Five out of 7 patients harboring the V600E BRAF mutation were treated with a BRAF inhibitor in different clinical trials. One mutated patient could not be treated due to exclusion criteria related to an underlying condition (terminal renal failure requiring chronic hemodialysis) and one patient received allogeneic stem-cell transplantation at relapse. No BRAF mutation was detected in the 13 newly diagnosed patients. Conclusion: Our results show that BRAF screening is feasible in routine practice and can help orienting therapy in relapsed/refractory MM patients. The incidence of 9.5% that we found in our series compares favorably with previously published results, and we observed a slightly increased incidence of 10.8% in the R/R population. The cell sorting technique seems to be more effective than the scraping technique for MM sample DNA acquisition and BRAF mutation screening. Results of BRAF inhibitors therapy in MM are eagerly awaited. Disclosures Lacroix: sanofi: Research Funding; qiagen: Membership on an entity's Board of Directors or advisory committees; roche: Membership on an entity's Board of Directors or advisory committees; astrazeneca: Membership on an entity's Board of Directors or advisory committees. Michot:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Ribrag:ArgenX: Research Funding; Esai: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; NanoString: Membership on an entity's Board of Directors or advisory committees.

Download Full-text

BIOM-17. BRAF MUTATION IS AN EARLY EVENT IN THE EVOLUTION OF A SUBSET OF GLIOBLASTOMAS AND IS ASSOCIATED WITH INCREASED PD-L1 EXPRESSION

Neuro-Oncology ◽

10.1093/neuonc/noaa215.017 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii5-ii5

Author(s):

Kyle Walsh ◽

Joanne Xiu ◽

Giselle López ◽

Daniel Landi ◽

Zachary Reitman ◽

...

Keyword(s):

Braf Mutation ◽

Braf V600e ◽

Early Event ◽

Low Grade ◽

Fusion Partner ◽

Wild Type ◽

Braf Mutations ◽

Durable Response ◽

Response Profile ◽

Glioneuronal Tumors

Abstract INTRODUCTION BRAF is a RAF-family kinase that regulates MAPK/ERK signaling. Activating BRAF mutations, including V600E, are common in circumscribed low-grade gliomas of childhood and young adulthood, but are uncommon in infiltrative astrocytomas, including glioblastoma. Their role in glioblastoma initiation and progression requires analysis of large datasets given the low frequency (1.0%) in TCGA IDH-wild-type glioblastomas. METHODS Molecular profiling was done on 4679 FFPE gliomas by next-generation sequencing at Caris Life Sciences, of which 3170 underwent RNA-sequencing for gene fusion and 4603 DNA-sequencing for mutations. MGMT promoter methylation was tested by pyrosequencing and PD-L1 IHC was performed using the SP142 clone. RESULTS Excluding variants of uncertain significance, BRAF mutations/fusions were most common in pleomorphic xanthoastrocytoma (PXA; N=12/24, 50%), glioneuronal tumors (N=6/13, 46%), pilocytic astrocytoma (PA; N=15/48, 31%), and ganglioglioma (n=5/18, 28%). BRAF fusions were uncommon (N=17), most frequent in PA (N=8/31, 26%) where they were associated with older age at daignosis (P=0.043), and typically involved KIAA1549 as fusion partner (70%). BRAF-mutated/fused glioblastoma patients (N=59/3126, 2%) were younger than BRAF-wild-type glioblastoma patients (54 versus 59 years, P=3.5x10-3); more likely to be MGMT-unmethylated (75% versus 56%, P=5.0x10-3); and 3x more likely to express PD-L1 (55% versus 17%, P=2.1x10-10). In tumors harboring a V600E mutation, the variant allele frequency (VAF) was similar in glioblastoma as in PXA, PA, ganglioglioma, and glioneuronal tumors (median VAF=35%). CONCLUSIONS BRAF-mutated glioblastoma were 3x more likely to express PD-L1 than BRAF-wild-type glioblastoma. We observed no differences in BRAF V600E clonality in BRAF-mutated glioblastoma compared to BRAF-mutated PXA, PA, ganglioglioma, and glioneuronal tumors, suggesting BRAF mutation is an initiating event in the clonal evolution of a subset of glioblastoma. There is rationale to evaluate combined BRAF inhibition with checkpoint inhibition in BRAF-mutated glioblastoma, potentially synergizing the complete response profile of the former with the durable response profile of the latter.

Download Full-text

CS-03 BRAF V600E mutation mediates FDG-methionine uptake mismatch in polymorphous low-grade neuroepithelial tumor of the young

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.089 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii20-ii20

Author(s):

Takahiro Hayashi ◽

Kensuke Tateishi ◽

Naoki Ikegaya ◽

Naoko Udaka ◽

Jo Sasame ◽

...

Keyword(s):

Mapk Pathway ◽

Positron Emission Tomography Imaging ◽

Mapk Signaling ◽

Braf V600e Mutation ◽

Mitogen Activated Protein Kinase ◽

Braf V600e ◽

Low Grade ◽

Protein Levels ◽

Positron Emission ◽

Methionine Uptake

Abstract We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11 C-methionine uptake and a region with homogenous low 18 F- fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated PLNTY (polymorphous low-grade neuroepithelial tumor of the young). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1) and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to BRAF V600E mutation and subsequent activation of MAPK signaling. Pharmacological inhibition of the MAPK pathway suppressed LAT1 expression and cell viability in PLNTY cells. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.

Download Full-text

LGG-23. EXCELLENT CLINICAL / RADIOLOGICAL RESPONSE TO BRAF INHIBITION IN A YOUNG CHILD WITH IN-OPERABLE SUPRA-SELLAR PILOCYTIC ASTROCYTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.405 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii370-iii371

Author(s):

Stacy Chapman ◽

Demitre Serletis ◽

Colin Kazina ◽

Mubeen Rafay ◽

Sherry Krawitz ◽

...

Keyword(s):

Targeted Therapy ◽

Pilocytic Astrocytoma ◽

Clinical Symptoms ◽

Obstructive Hydrocephalus ◽

Braf V600e Mutation ◽

Braf V600e ◽

Low Grade ◽

Dramatic Improvement ◽

Chemotherapeutic Regimen ◽

Response To Chemotherapy

Abstract In-operable low grade gliomas (LGG) in the pediatric population continue to present a treatment dilemma. Due to the low-grade nature of these tumors, and variable response to chemotherapy / radiation, the choice of adjuvant treatment is difficult. Overall survival is directly related to the degree of surgical resection, adding complexity to these inoperable tumors. Current chemotherapeutic regimen for these inoperable tumors includes vincristine (VCR) and carboplatin (Carbo). With advancements in the molecular characterization of gliomas, the role of targeted therapy has come into question. We present a 2-year-old female with biopsy proven Pilocytic Astrocytoma (positive BRAF-V600E mutation) involving the hypothalamic/optic chiasm region. She presented with ataxic gait, bi-temporal hemianopia, obstructive hydrocephalus and central hypothyroidism, which progressed to altered consciousness, and right hemiparesis due to location/mass effect of the tumor. She was initially treated with chemotherapy (VCR/Carbo) but her tumor progressed at 6 weeks of treatment. As her tumor was positive for BRAF-V600E mutation, she was started on Dabrafenib monotherapy, resulting in dramatic improvement in her clinical symptoms (able to stand, improved vision), and a 60% reduction in tumor size at 3-months. At 6-months, follow up MRI showed slight increase in the solid portion of the tumor, with no clinical symptoms. We plan to add MEK inhibitor (Trametinib) and continue with Dabrafenib. Our experience and literature review suggests that LGG with BRAF-V600E mutations may benefit from upfront targeted therapy. Prospective clinical trials comparing the efficacy of BRAF inhibitors versus standard chemotherapy in LGG with BRAF mutations are urgently needed.

Download Full-text

Treatment of a BRAF V600E Positive Ameloblastoma in a Pediatric Patient with MEK Inhibitor Monotherapy

FACE ◽

10.1177/27325016211005126 ◽

2021 ◽

pp. 273250162110051

Author(s):

Steven Daws ◽

Kongkrit Chaiyasate ◽

Arshi Lehal

Keyword(s):

Mapk Pathway ◽

Case Reports ◽

Radical Resection ◽

Mek Inhibitor ◽

Braf V600e Mutation ◽

Braf V600e ◽

Targeted Chemotherapy ◽

Odontogenic Epithelium ◽

Genetic Landscape ◽

Frequent Presence

Ameloblastomas are uncommon tumors of the odontogenic epithelium standardly treated with radical resection. Recent studies of the genetic landscape of ameloblastoma have revealed the frequent presence of the BRAF V600E mutation, suggesting a possible role for targeted chemotherapy. We present the case of a primary mandibular ameloblastoma found in a 13-year-old female with confirmed BRAF V600E mutation. Prior to invasive surgical intervention she was treated for 8 weeks with the MEK inhibitor trametinib, but her tumor demonstrated little radiographic, clinical, or histologic response. Previous case reports have shown ameloblastoma in adult patients to be responsive to other agents targeting the MAPK pathway. Our observations in the presented case demonstrate the need for further research into the utility of targeted chemotherapy in ameloblastoma treatment.

Download Full-text