Mutations of the BRAF gene in human cancer

@article{Davies2002MutationsOT,
  title={Mutations of the BRAF gene in human cancer},
  author={H. Davies and Graham Bignell and Charles Cox and Philip J. Stephens and Sarah Edkins and Sheila Clegg and Jon W. Teague and Hayley B Woffendin and Mathew J. Garnett and William E. Bottomley and Neil Davis and E. Dicks and Rebecca Ewing and Yvonne Floyd and Kristian A. Gray and Sarah Hall and Rachel Hawes and Jaime Hughes and Vivian Kosmidou and Andrew Menzies and Catherine Mould and Adrian Parker and Claire H Stevens and Stephen Watt and Steven Hooper and Rebecca Wilson and Hiran Jayatilake and Barry Gusterson and Colin S Cooper and Janet M Shipley and Darren R. Hargrave and Kathy Pritchard-Jones and Norman J. Maitland and Georgia Chenevix-Trench and Gregory J Riggins and Darell D. Bigner and Giuseppe Palmieri and Antonio Cossu and Adrienne M. Flanagan and Andrew G. Nicholson and Judy W. C. Ho and Suet Yi Leung and Siu Tsan Yuen and Barbara L. Weber and Hilliard F. Seigler and Timothy L. Darrow and Hugh E Paterson and Richard M. Marais and Christopher J. Marshall and R. Wooster and Michael R. Stratton and P. Andrew Futreal},
  journal={Nature},
  year={2002},
  volume={417},
  pages={949-954}
}
Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS–RAF–MEK–ERK–MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF… 
Mutations of the BRAF gene in human cancer, by Davies et al. (Nature 2002; 417: 949–54)
TLDR
The most significant breakthrough has led from the original Davies et al. paper has been the development of a specific monoclonal antibody to BRAF V600E, vemurafenib, found to improve survival at 6 months compared with more standard chemotherapy, with survival rates of 84% and 64%, respectively.
Emerging BRAF Mutations in Cancer Progression and Their Possible Effects on Transcriptional Networks
TLDR
The influence of various BRAF mutations in cancer, including aberrant transcriptional gene regulation in the affected tissues are discussed, including chromatinocyte proliferation and invasion enhanced in cancer patients with such mutations.
Mouse models for BRAF-induced cancers.
TLDR
The data so far obtained following Cre-mediated activation in haemopoietic tissue and the lung indicate that (V600E)BRAF mutation can drive tumour initiation and that its primary effect is to induce high levels of cyclin D1-mediated cell proliferation.
Mutational analysis of the BRAF gene in human tumor cells
TLDR
The present results suggest that BRAF may not be a frequent target of mutations involved in the pathogenesis of human lung, breast, kidney, cervical, endometrial and ovarian carcinomas.
BRAF and KRAS mutations in stomach cancer
TLDR
The data indicate that BRAF is occasionally mutated in stomach cancer, and suggest that alterations of RAS pathway both by RAS and BRAF mutations contribute to the pathogenesis of stomach cancer.
Mutational analysis of the ARAF gene in human cancers
TLDR
The data indicate that, in contrast to the BRAF gene, the ARAF gene is rarely mutated in human cancers, and suggest that alterations of the RAS pathway by ARAf gene mutation may not play an important role in the pathogenesis of human cancers.
BRAF: From Discovery to Drug Resistance
TLDR
The BRAF gene encodes a protein in the Mitogen-Activated Protein Kinase (MAPK) pathway which regulates several important cellular functions, including proliferation, differentiation, migration, and apoptosis, and under normal circumstances the MAPK pathway is triggered when extracellular signals activate receptor tyrosine kinases and G-protein-coupled receptors.
Hitting the Target in BRAF-Mutant Colorectal Cancer.
  • Ankur K Nagaraja, A. Bass
  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2015
TLDR
Pharmacodynamic studies are essential to validate that a drug inhibits its intended target within tumor cells in the human host and that this interaction causes sustained downregulation of signaling through the relevant oncogenic pathway.
Mutations of BRAF and RAS are rare events in germ cell tumours
TLDR
The finding of activated Erk suggests a causative role for MAPK activation in GCT independent of activating BRAF or RAS mutations, and may be linked to the proficiency of these tumours in repairing mismatched bases in DNA.
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