|
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 |
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 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 |
The activating V599E mutation accounted for 80% of all mutations detected in cutaneous melanoma cell lines.
|
12917419 |
2003 |
|
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 |
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 |
|
rs121913227
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
In addition, a double mutation resulting in V599K substitution was detected in two suspect ocular metastases of cutaneous melanoma.
|
14522889 |
2003 |
|
rs113488022
|
|
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 |
|
rs113488022
|
|
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 |
|
rs113488022
|
|
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 |
|
rs113488022
|
|
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 |
|
rs113488022
|
|
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 |
|
rs113488022
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The activating V599E mutation accounted for 80% of all mutations detected in cutaneous melanoma cell lines.
|
12917419 |
2003 |
|
rs113488022
|
|
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 |
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 |
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 |
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 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 |
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 |
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 |
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 |
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 |
Among 13 lesions with structural changes, BRAF(V599E) mutations were found in 4 (3 melanomas</span> and 1 nevus).
|
15373778 |
2004 |