|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi.
|
12447372 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
In addition we have searched for exon 15 BRAF mutations in 24 samples of secondary melanoma from 22 cases of sporadic melanoma and detected the 1796T>A BRAF mutation which leads to a substitution of valine by glutamic acid at position 599 (V599E) in six samples.
|
12619120 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We investigated the hypothesis that this common somatic BRAF mutation (V599E) would contribute to melanoma predisposition in familial and polygenic malignant melanoma if occurring as a germ-line mutation.
|
12794760 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The activating V599E mutation accounted for 80% of all mutations detected in cutaneous melanoma cell lines.
|
12917419 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Thus, when present, BRAF(V599E) appears to be essential for melanoma cell viability and transformation and, therefore, represents an attractive therapeutic target in the majority of melanomas that harbor the mutation.
|
14500344 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Mutations in the BRAF gene causing a V599E amino acid substitution that enhance the kinase activity have been described in >60% of cutaneous melanomas and premalignant melanocytic lesions.
|
14522889 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The most common mutation in CM was V599E, but a novel point mutation (L596Q) was identified in two cases and an in-frame deletion/insertion (VKSRWK599-604D) was discovered in one case.
|
14522897 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We have examined the role of oncogenic B-RAF in the early stages of melanoma by expressing (V599E)B-RAF in cultured melanocytes.
|
15059882 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Tumor-specific tandem mutations, encoding either V599K, V599R, or V599E, were found in 5 of 17 (29%) melanomas with BRAF exon 15 mutations.
|
15140228 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The most common mutation, occurring in 80% of cutaneous melanoma samples, is a T-to-A transition resulting in a single amino acid substitution (V599E).
|
15179189 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14(ARF) in these cell lines, and found one NRAS mutation and three p16/p14(ARF) mutations.
|
15191558 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Interestingly, the mutated BRAF (V599E)-specific siRNA inhibited the growth and MAPK activity of only melanoma cell lines with this mutation.
|
15208655 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The T1799A (V600E) mutation was detected by sequencing in melanomas from 5 of 22 patients as well as in the positive control, a cutaneous melanoma cell line.
|
15277467 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The loss of the (V599E)BRAF genotype during progression from primary to metastatic melanoma in patients with (V599E)BRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.
|
15289355 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
To identify such contributing factors, we used microarray gene expression profiling to screen for differences in gene expression between a panel of melanocytic and melanoma cell lines with WT BRAF and a group of melanoma cell lines with the V599E BRAF mutation.
|
15313890 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
With respect to the B-raf protein sequence, the V599E mutation was predicted in 63% of these positive melanomas, followed in frequency by the V599K transition (31%).
|
15331929 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Among 13 lesions with structural changes, BRAF(V599E) mutations were found in 4 (3 melanomas</span> and 1 nevus).
|
15373778 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
With regard to the frequency of V599E BRAF mutations, AM significantly differs from CM (P < or = .0001), which suggests that BRAF mutations distinguish anorectal from cutaneous melanoma at the molecular level.
|
15578519 |
2004 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Absence of V599E BRAF mutations in desmoplastic melanomas.
|
15641040 |
2005 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We were able to detect the V599E mutation in genomic DNA from paraffin-embedded melanoma samples and could routinely detect this mutation in fine-needle aspirations of melanoma tumors.
|
15737846 |
2005 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We studied global gene expression in three melanoma cell lines with the most common and potent V600E mutation in the B-RAF gene-four cell lines with a common Q61R mutation in the N-RAS gene and three cell lines with no mutations using human HG-U133A 2.0 micro-arrays with 22 277 transcripts.
|
15760917 |
2005 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Thus, these studies identify the mechanistic underpinnings by which mutant (V599E)B-RAF promotes melanoma development and show the effectiveness of targeting this protein to inhibit melanoma tumor growth.
|
15781657 |
2005 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The absence of the BRAF V600E mutation in Spitz's nevi may serve as a molecular signature to distinguish these lesions from common nevi, dysplastic nevi, and some types of malignant melanoma.
|
15811117 |
2005 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Unexpectedly, V599 and V599E mutations were absent in cutaneous/subcutaneous metastases derived from acrolentiginous melanomas as preceding primary tumours.
|
15935100 |
2005 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Ectopic MITF expression in conjunction with the BRAF(V600E) mutant transformed primary human melanocytes, and thus MITF can function as a melanoma oncogene.
|
16001072 |
2005 |