A screening test for BRAF mutant melanoma: Immunohistochemical (IHC) analysis of BRAF V600E mutation.

e15547 Background: BRAF V600E mutation is associated with poor prognosis in patients with metastatic colorectal cancer (mCRC), while the non-V600E mutation mCRC patients showed better prognosis than that of V600E mutation. The clinicopathologic features between V600E and non-V600E mutation has not yet been fully evaluated. And the impact of metastasectomy for patients with BRAF-mutant mCRC was not well-known. Methods: A retrospective study was conducted to evaluate the clinical and pathological characteristics of patients with BRAF-mutant mCRC. Next generation sequencing (22-gene panel) was performed in some of the patients. Survival was also analyzed in the cohort of BRAF V600E and non-V600E mutation with or without metastasectomy. Results: Between December 2014 and August 2020, 116 patients with BRAF-mutant mCRC were enrolled, including 94 patients with BRAF V600E mutation and 22 patients with non-V600E mutation. Significant difference was observed in the prevalence of peritoneal metastasis (69.1% vs. 27.3%, P = 0.001) and lung metastasis (11.7% vs. 36.4%, P = 0.009) between BRAF V600E mutation and non-V600E mutations. In genomic profile, SMAD4 mutation (30.7% vs. 13.7%) showed higher prevalence in patients with BRAF V600E mutation than that of non-V600E mutations, while RAS mutation (18.2% vs. 6.4%) and FBXW7 mutation (13.7% vs 3.1%) had higher incidence in BRAF non-V600E mutations than that of V600E mutation. Patients with BRAF V600E mutation showed a poorer overall survival than those with non-V600E mutations (13.9 vs. 26.8 months, P = 0.038). Totally, 46 patients received metastasectomy after systemic treatment. The median survival for BRAF V600E patients with or without metastasectomy was not reach (42.3+ months) vs. 8.3 months, respectively ( P < 0.001), and for non-V600E patients with or without metastasectomy was not reach (64.2+ months) vs. 23.3 months, respectively (P < 0.001). In multivariate analysis, ECOG performance status (0-1 vs. 2) ( P = 0.001), Staging (IVa-b vs. IVc) ( P = 0.01) and metastasectomy ( P = 0.001) were independent prognostic factors of overall survival. Conclusions: BRAF V600E mutation defines a subgroup of mCRC with worse prognosis. Metastasectomy might improve the survival benefit in carefully selected BRAF-mutant mCRC patients after systemic treatment.

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Efficacy and tolerability of vemurafenib in BRAF-mutant acral and mucosal melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e21017 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e21017-e21017

Author(s):

Xue Bai ◽

Lu Si ◽

Zhihong Chi ◽

Xinan Sheng ◽

Chuanliang Cui ◽

...

Keyword(s):

Adverse Effects ◽

Survival Data ◽

Survival Curve ◽

Similar Efficacy ◽

Mucosal Melanoma ◽

Braf V600e Mutation ◽

Braf V600e ◽

Efficacy And Safety ◽

Hand Foot Syndrome ◽

Braf Mutant

e21017 Background: Vemurafenib has substantially impressive clinical efficacy in cutaneous melanoma (CM). However, compared with their cutaneous counterpart, acral melanoma (AM) and mucosal melanoma (MM) have distinct genetic patterns and worse prognosis. The efficacy and safety profiles of vemurafenib in AM and mm remain unclear. Methods: Clinical, pathological, and therapeutic data were collected and reviewed of patients (pts) with metastatic or unresectable BRAF-mutant AM and mm hospitalized and administrated vemurafenib during January 2011 and January 2017. Responses were evaluated by RECIST v1.1, survival data were analyzed by Kaplan-Meier survival curve, and adverse effects were assessed by CTCAE v4.0. Results: 24 pts were identified, 13 (54.2%) with AM, 11 (45.8%) with mm (1 patient without available radiology data). All 13 AM pts harbored BRAF V600E mutation (1 with simultaneous C-KIT E861K mutation); 10/11 (90.9%) mm pts carried BRAF V600E mutation (1 with simultaneous PDGFRA V824I mutation), 1/11 (9.1%) had BRAF D594N mutation. Median PFS were 5.4 (95%CI 3.5-8.7) and 4.5 (95%CI 1.5-15.0) months, median OS were 11.7 (95%CI 8.1-23.6) and 7.9 (95%CI 4.6-26.2) months; ORRs were 61.5% (8/13) and 40.0% (4/10), DCRs were 92.3% (12/13) and 90.0% (9/10) in AM and MM, respectively. Vemurafenib was well tolerated. The most common adverse effects (AEs) were hand-foot syndrome in AM and elevation of total cholesterol in MM, with the incidence of 23.1% (3/13) and 18.2% (2/11), respectively. Grade 3/4 AEs have not been observed. No patient discontinued vemurafenib because of treatment related toxicity. Conclusions: Vemurafenib yields substantial response in pts with AM and MM. Compared with in CM, vemurafenib has similar efficacy and safety profiles in BRAF-mutant AM and MM.

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Blood-Based Detection of BRAF V600E in Gliomas and Brain Tumor Metastasis

Cancers ◽

10.3390/cancers13061227 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1227

Author(s):

Keiko M. Kang ◽

Koushik Muralidharan ◽

Anudeep Yekula ◽

Julia L. Small ◽

Zachary S. Rosh ◽

...

Keyword(s):

Brain Metastasis ◽

Tumor Metastasis ◽

Disease Status ◽

Braf V600e Mutation ◽

Braf V600e ◽

Healthy Control ◽

Small Patient ◽

Hotspot Mutations ◽

Braf Mutant

Liquid biopsy provides a minimally invasive platform for the detection of tumor-derived information, including hotspot mutations, such as BRAF V600E. In this study, we provide evidence of the technical development of a ddPCR assay for the detection of BRAF V600E mutations in the plasma of patients with glioma or brain metastasis. In a small patient cohort (n = 9, n = 5 BRAF V600E, n = 4 BRAF WT, n = 4 healthy control), we were able to detect the BRAF V600E mutation in the plasma of 4/5 patients with BRAF V600E-tissue confirmed mutant tumors, and none of the BRAF WT tumors. We also provide evidence in two metastatic patients with longitudinal monitoring, where the plasma-based BRAF V600E mutation correlated with clinical disease status. This proof of principle study demonstrates the potential of this assay to serve as an adjunctive tool for the detection, monitoring, and molecular characterization of BRAF mutant gliomas and brain metastasis.

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LGG-05. GENERATION OF NOVEL MOUSE MODELS FOR BRAF V600E MUTANT GLIOMAGENESIS TO GAIN MECHANISTIC INSIGHTS INTO TUMOR FORMATION AND PROGRESSION

Neuro-Oncology ◽

10.1093/neuonc/noab090.129 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i32-i32

Author(s):

Claudia K. Petritsch ◽

Anne Marie Barrette ◽

Jong-Whi Park

Keyword(s):

Mouse Models ◽

Mutant Mouse ◽

Tumor Formation ◽

Genetically Engineered ◽

Braf V600e Mutation ◽

Braf V600e ◽

Common Mutation ◽

Low Grade ◽

Braf Mutant

Abstract Background The BRAF V600E mutation occurs in ~ twenty percent of histologically diverse pediatric gliomas and is the second most common mutation in pediatric low-grade gliomas (LGG). BRAF V600E expression in LGG with balanced CDKN2A is associated with a higher rate for progression than for BRAF V600E wildtype tumors, and despite adjuvant therapy, consisting of resection, radiation and chemotherapy. Progression invariably occurs in BRAF V600E mutant CDKN2A deleted gliomas, marking a high-risk group. Here, we aim to overcome the lack BRAF V600E mutant glioma models that allow for studies of stem and progenitor cells and the immune system ability to understand progression. Methods We develop novel immunocompetent, stem and progenitor cell-based mouse models for BRAF mutant gliomas, including genetically engineered mouse models (GEMMs), orthotopic glioma models derived from gliomas in GEMMs as well as in vitro models of those tumors. BRAF mutant mouse brains and cells were analyzed by immunofluorescence staining, flow cytometry, mass cytometry and RNA sequencing. Results Ongoing model development studies indicate that BRAF V600E mutant gliomas in murine brain exhibit very similar neuroanatomical preferences to human gliomas. The BRAF V600E mutation exacerbates the heterogenous cell cycling pattern of normal neural stem and progenitors and expands a symmetrically dividing progenitor population. Cellular plasticity rather than cellular lineage hierarchy drives the generation of a therapy resistant stem cell pool. Transcriptomic analyses of neuroglial stem cells with induced BRAF V600E expression provide insights into mechanisms for neoplastic transformation and progression. Conclusion Analyses of two independent BRAF V600E mutant mouse models provide novel insights into the role for tumor intrinsic factors, such as plasticity and stemness, and the tumor microenvironment in progression.

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BRAF-mutant melanoma of the skin during pregnancy with dichorionic diamniotic twins. Clinical case

MD-Onco ◽

10.17650/2782-3202-2021-1-1-38-42 ◽

2021 ◽

Vol 1 (1) ◽

pp. 38-42

Author(s):

M. M. Davydov ◽

P. A. Zeynalova ◽

A. A. Fedenko ◽

D. A. Chekiny ◽

E. K. Ibragimov ◽

...

Keyword(s):

Lymph Node ◽

Clinical Case ◽

Retrospective Studies ◽

Braf V600e Mutation ◽

Braf V600e ◽

Malignant Neoplasms ◽

Node Dissection ◽

Child Bearing ◽

Braf Mutant ◽

Conclusive Data

Per the majority of authors, melanoma is the most common tumor diagnosed during pregnancy (31 % of all malignant neoplasms). In approximately 1/3 of women melanoma developed in child-bearing age is diagnosed during pregnancy or in the postpartum period. However, only some retrospective studies analyzed the effect of pregnancy on melanoma development, and conclusive data on development, progression and treatment of BRAF-mutant melanoma is lacking. In this subpopulation of patients, BRAF status supposedly can negatively affect disease outcome irrespective of treatment methods.The article presents a clinical case of recurrence of melanoma with the BRAF V600E mutation during pregnancy. The patient underwent lymph node dissection during pregnancy prolongation, after labor she received antitumor drug therapy with МЕК and ВRAF inhibitors. Melanoma recurrence during pregnancy did not worsen treatment outcomes for the mother and embryo.

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Detection of the BRAF V600E mutation in melanocytic lesions using the ligase detection reaction

Yearbook of Pathology and Laboratory Medicine ◽

10.1016/s1077-9108(08)70313-x ◽

2007 ◽

Vol 2007 ◽

pp. 100-101

Author(s):

D.M. Jukic

Keyword(s):

Braf V600e Mutation ◽

Braf V600e ◽

Ligase Detection Reaction ◽

Melanocytic Lesions

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Therapie des BRAF-mutierten NSCLC

Onkologische Welt ◽

10.1055/s-0038-1677603 ◽

2018 ◽

Vol 09 (05) ◽

pp. 239-239

Author(s):

Dr. Susanne Krome

Keyword(s):

Phase Ii ◽

Braf V600e Mutation ◽

Braf V600e ◽

Alk Rearrangement

BRAF-mutierte nicht kleinzellige Bronchialkarzinome (NSCLC) sind besonders aggressiv. Gezielte Antikörpertherapien verbesserten die Behandlungsergebnisse. Bei einem ALK-Rearrangement ging eine lange progressionsfreie Zeit nicht zu Lasten der Post-Progressionsphase. Die Sekundäranalyse einer nicht randomisierten Phase-II-Studie zeigt dies nun auch für Patienten mit einer BRAF-V600E-Mutation.

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