Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (24112705)
Authors Wagenaar TR, Ma L, Roscoe B, Park SM, Bolon DN, Green MR
Title Resistance to vemurafenib resulting from a novel mutation in the BRAFV600E kinase domain.
Journal Vol Issue Date Pages Journal Short Title
Pigment cell & melanoma research 27 1 2014 Jan 124-33 Pigment Cell Melanoma Res
URL
Abstract Text Resistance to the BRAF inhibitor vemurafenib poses a significant problem for the treatment of BRAFV600E-positive melanomas. It is therefore critical to prospectively identify all vemurafenib resistance mechanisms prior to their emergence in the clinic. The vemurafenib resistance mechanisms described to date do not result from secondary mutations within BRAFV600E. To search for possible mutations within BRAFV600E that can confer drug resistance, we developed a systematic experimental approach involving targeted saturation mutagenesis, selection of drug-resistant variants, and deep sequencing. We identified a single nucleotide substitution (T1514A, encoding L505H) that greatly increased drug resistance in cultured cells and mouse xenografts. The kinase activity of BRAFV600E/L505H was higher than that of BRAFV600E, resulting in cross-resistance to a MEK inhibitor. However, BRAFV600E/L505H was less resistant to several other BRAF inhibitors whose binding sites were further from L505 than that of PLX4720. Our results identify a novel vemurafenib-resistant mutant and provide insights into the treatment for melanomas bearing this mutation.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
BRAF F516G missense unknown BRAF F516G lies within the protein kinase domain of the Braf protein (UniProt.org). F516G has been identified in the scientific literature (PMID: 24112705), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, Sep 2025).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF L505H BRAF V600E Advanced Solid Tumor resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing BRAF V600E and L505H was resistant to Zelboraf (vemurafenib) treatment in culture (PMID: 24112705). 24112705
BRAF L505H BRAF V600E Advanced Solid Tumor decreased response RAF265 Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing BRAF V600E and L505H was less sensitive to RAF265 treatment compared to cells expressing BRAF V600E alone in culture (PMID: 24112705). 24112705
BRAF L505H BRAF V600E Advanced Solid Tumor decreased response SB590885 Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing BRAF V600E and L505H was less sensitive to SB590885 treatment compared to cells expressing BRAF V600E alone in culture (PMID: 24112705). 24112705
BRAF L505H BRAF V600E melanoma resistant RAF265 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing L505H was resistant to RAF265 treatment in culture (PMID: 24112705). 24112705
BRAF L505H BRAF V600E Advanced Solid Tumor resistant PLX4720 Preclinical Actionable In a preclinical study, a cell line expressing BRAF V600E and L505H was resistant to PLX4720 treatment in culture and in a transplant mouse model (PMID: 24112705). 24112705
BRAF L505H BRAF V600E Advanced Solid Tumor decreased response GDC0879 Preclinical - Cell culture Actionable In a preclinical study, a cell line expressing BRAF V600E and L505H was less sensitive to GDC0879 treatment compared to cells expressing BRAF V600E alone in culture (PMID: 24112705). 24112705
BRAF T529N BRAF V600E melanoma predicted - resistant PLX4720 Preclinical - Cell culture Actionable In a preclinical study, PLX4720 inhibited Mek phosphorylation in a melanoma cell line harboring BRAF V600E and BRAF T529N, however, did not inhibit viability in culture (PMID: 24112705). 24112705
BRAF L505H BRAF V600E melanoma resistant PLX4720 Preclinical - Cell culture Actionable In a preclinical study, melanoma cell lines harboring BRAF V600E and expressing L505H were resistant to PLX4720 in culture (PMID: 24112705). 24112705
BRAF F516G BRAF V600E melanoma sensitive U0126 Preclinical - Cell culture Actionable In a preclinical study, U0126 inhibited Erk phosphorylation and downstream signaling and viability in a melanoma cell line harboring BRAF V600E and expressing BRAF F516G in culture (PMID: 24112705). 24112705
BRAF F516G BRAF V600E melanoma resistant PLX4720 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing F516G was resistant to PLX4720 in culture (PMID: 24112705). 24112705
BRAF L505H BRAF V600E melanoma resistant SB590885 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing L505H was resistant to SB590885 treatment in culture (PMID: 24112705). 24112705
BRAF T529N BRAF V600E melanoma sensitive U0126 Preclinical - Cell culture Actionable In a preclinical study, U0126 inhibited Erk phosphorylation and downstream signaling and viability in a melanoma cell line harboring BRAF V600E and expressing BRAF T529N in culture (PMID: 24112705). 24112705
BRAF L505H BRAF V600E melanoma resistant U0126 Preclinical - Cell culture Actionable In a preclinical study, a melanoma cell line harboring BRAF V600E and expressing L505H was resistant to U0126 treatment in culture (PMID: 24112705). 24112705