Melanomagenesis driven by a kinase-dead mutant BRAF lacking codons 600-618
Girtman, M. A.; Richmond, C. S.; Campbell, M. E.; Rehrauer, W. M.; Kenny, P.
Show abstract
While considerable success has been achieved with treating BRAF-V600E mutant tumors in several organ systems, tumors expressing non-V600E BRAF mutations remain a significant clinical challenge. Such atypical BRAF mutations are classified based on their kinase activity, RAS-dependence and their requirement for dimerization to function. We identified an unusually large in-frame deletion in a melanoma patient, encompassing codons 600-618 in the kinase domain. This patient experienced rapid disease progression when treated with dual BRAF/MEK inhibition. To determine whether and how such a large in-frame BRAF deletion might be activating, we ectopically expressed it in HEK293 cells and monitored BRAF pathway activation and response to BRAF and MEK inhibitors. We demonstrate that this mutation results in a kinase-deficient BRAF mutant which, nevertheless, activates MEK/ERK signaling in a dimerization-dependent manner, placing this mutation among the class III BRAF mutants.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines 92%
- The TLK1-MK5 axis regulates motility, invasion, and metastasis of prostate cancer cells 91%
- Multiple ETS Factors Participate in the Transcriptional Control of TERT Mutant Promoter in Thyroid Cancers 90%
Similar papers in this journal
- Identification of Hsp90 inhibitors as potential drugs for the treatment of TSC1/TSC2 deficient cancer 92%
- CTDSP1 inhibitor rabeprazole regulates DNA-PKcs dependent topoisomerase I degradation and irinotecan drug resistance in colorectal cancer 91%
- Merlin Tumor Suppressor Function is Regulated by PIP2-Mediated Dimerization 90%
Similar papers in this journal
- Characterization of clostridium botulinum neurotoxin serotype A (BoNT/A) and fibroblast growth factor receptor interactions using a novel receptor dimerization assay 90%
- High-Throughput Kinase Inhibitor Screening Reveals Roles for Aurora and Nuak Kinases in Neurite Initiation and Dendritic Branching 90%
- Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27 90%
Similar papers in this journal
- Quantifying small GTPase activation status using a novel fluorescence HPLC-based assay 90%
- Fluorescent tagging of endogenous IRS2 with an auxin-dependent degron to assess dynamic intracellular localization and function 89%
- Cell entry of SARS-CoV-2 conferred by angiotensin-converting enzyme 2 (ACE2) of different species 89%
Similar papers in this journal
- Kinase Suppressor of RAS 1 (KSR1) maintains the transformed phenotype of BRAFV600E mutant human melanoma cells 91%
- Optimized transcriptional signature for evaluation of MEK/ERK pathway baseline activity and long-term modulations in ovarian cancer 91%
- Suitability of GRK antibodies for individual detection and quantification of GRK isoforms in western blots 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.