|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Cases of pediatric LCH with long-term follow-up from our institution were analyzed for mutations in BRAF<sup>V600</sup> and MAP2K1 exons 2 and 3 by immunostaining with mutation-specific VE1 antibody, as well as allele-specific PCR and sequencing, respectively.
|
30923995 |
2019 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
LCH samples showed mutually exclusive mutations of BRAF (8/20) and MAP2K1 (4/19), but no mutation of KMT2D, NRAS nor NOTCH1.
|
29194093 |
2018 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Genomic characterization has identified activating point mutations including mutually exclusive BRAFV600E and activating MAP2K1 mutations to be responsible for ERK activation in a majority of pediatric LCH patients.
|
28748614 |
2018 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We evaluated a patient with treatment-refractory LCH for mutations in the RAS-RAF-MEK-ERK pathway and identified a novel mutation in the MAP2K1 gene resulting in a p.L98_K104 > Q deletion and predicted to be auto-activating.
|
29768711 |
2018 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
We assessed for BRAF and MAP2K1 mutations in seven cases of Langerhans cell histiocytosis detected incidentally in biopsies involved by lymphoma.
|
28084334 |
2017 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
To the differentiation-related markers, the BRAF/MAP2K1-mut LCH expressed CD14 but rarely expressed CD83 or CD86 (P < .001).
|
27597420 |
2017 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In agreement with 2 recent studies, we showed a high frequency of MAP2K1 mutations in BRAF-negative LCH cases.
|
26980021 |
2016 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this study, we attempted to identify other mutations which may explain the MAPK activation in nonmutated BRAF and MAP2K1 LCH lesions.We analysed 26 pulmonary and 37 nonpulmonary LCH lesions for the presence of BRAF, MAP2K1, NRAS and KRAS mutations.
|
27076591 |
2016 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
However, at least in the cases of LCH and ECD, there is a very high frequency of activating mutations in MAPK pathway genes, most notably BRAF-V600E, as well as MAP2K1, in LCH and NRAS in ECD.
|
26637772 |
2015 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis.
|
25899310 |
2015 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The recent discovery of somatic mutations in ARAF and in MAP2K1, which lead to activation of the RAS-RAF-MEK -ERK pathway in the setting of wild-type BRAF, as well as the finding that activating mutation in MAP2K1 are relatively insensitive to MEK inhibitors, suggest that a more detailed understanding of this pathway in LCH may be necessary for the development of more effective targeted therapies.
|
26637773 |
2015 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The mutually exclusive nature of MAP2K1 and BRAF mutations implicates a critical role of oncogenic MAPK signaling in LCH.
|
24982505 |
2014 |
|
Histiocytosis, Langerhans-Cell
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Notably, 33% (7/21) of LCH cases with wild-type BRAF and none (0/20) with BRAFV600E harbored somatic mutations in MAP2K1 (6 in-frame deletions and 1 missense mutation) that induced extracellular signal-regulated kinase (ERK) phosphorylation in vitro.
|
25202140 |
2014 |