Activating mutation of BRAF is a common finding in pediatric gliomas. As many as 14% of high grade and up to 66% of certain subtypes of low grade pediatric glioma have the BRAFV600E mutation. Small molecule inhibitors that selectively target BRAFV600E are FDA approved for melanoma and have shown significant efficacy in treating BRAFV600E glioma in pre-clinical trials. Despite showing initial an...

BACKGROUND The BRAFV600E mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). In recent studies, the BRAFV600E mutation has been associated with poor clinicopathological characteristics, such as lymph node metastasis, extrathyroidal extension, and advanced stage. However, other studies have failed to establish an association between the BRAFV600E mutation and cli...

Mutation specific immunohistochemistry (IHC) is a promising new technique to detect the presence of the BRAFV600E mutation in colorectal carcinoma (CRC). When performed in conjunction with mismatch repair (MMR) IHC, BRAFV600E IHC can help to further triage genetic testing for Lynch Syndrome. In a cohort of 1426 patients undergoing surgery from 2004 to 2009 we recently demonstrated that the comb...

Malignant melanoma is frequently driven by mutational activation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) accompanied by silencing of the phosphatase and tensin homology (PTEN) tumor suppressor. Despite the implied importance of PI3K signaling in PTENNull melanomas, mutational activation of the gene encoding the catalytic subunit of PI3Kα (PIK3CA), is rarely detected. Since PTEN...

Cross-feedback activation of MAPK and AKT pathways is implicated as a resistance mechanism for cancer therapeutic agents targeting either RAF/MEK or PI3K/AKT/mTOR. It is thus important to have a better understanding of the molecular resistance mechanisms to improve patient survival benefit from these agents. Here we show that BRAFV600E is a negative regulator of the AKT pathway. Expression of B...

Introduction Twenty-five - fifty percent of skin melanomas arise from nevi. Melanocyte proliferation is activated by BRAFV600E, then is arrested, but single nevi transform to melanomas. p16 controls arrest, and p16 loss may promote transformation. Aim To analyze BRAFV600E, p16 expression and melanocyte proliferation in dermal, compound and dysplastic nevi, cells of primary and metastatic mela...

In their recent Matters Arising, Scurr et al. (2010) questioned several of our conclusions regarding the role of IGFBP7 in BRAFV600E-mediated senescence induction. In our original study in Cell (Wajapeyee et al., 2008), we used a genome-wide RNA interference (RNAi) screen to identify 17 genes required for an activated BRAF oncogene (BRAFV600E) to block proliferation of primary melanocytes and m...

Langerhans cell histiocytosis (LCH) is a clinically and histologically heterogeneous disorder. Its classification as either reactive inflammatory or neoplastic has been a matter of debate. However, the recent finding of frequent BRAFV600E mutations in LCH argues for the latter. The exact cell type that harbors the mutation and is responsible for proliferation remains to be identified. We here a...

Treatment of BRAFV600E-mutant melanoma by small molecule inhibitors that target BRAFV600E or MEK kinases is increasingly used in clinical practice and significantly improve patient outcome. However, patients eventually become resistant and therapeutic improvement is required. Molecular diversity within individual tumors (intratumor heterogeneity) and between tumors within a single patient (intr...

Molecularly targeted therapeutics have revolutionized the treatment of BRAFV600E-driven malignant melanoma, but rapid development resistance to BRAF kinase inhibitors (BRAFi) presents a significant obstacle. Here, we describe identification experimental melanoma overcoming NRAS-based BRAFi-resistance employing stringent genetic model BRAFi-resistance, i.e. isogenic cell lines that differ only b...