Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Drug
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Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0278883 (
metastatic melanoma
)
6,224
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We sequenced eight melanoma exomes to identify new somatic mutations in
metastatic melanoma
. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or
MAP3K9
. Structural modeling predicted that mutations in the kinase domain may affect the activity and regulation of these protein kinases. The position of the mutations and the loss of heterozygosity of MAP3K5 and
MAP3K9
in 85% and 67% of melanoma samples, respectively, together suggest that the mutations are likely to be inactivating. In in vitro kinase assays, MAP3K5 I780F and
MAP3K9
W333* variants had reduced kinase activity. Overexpression of MAP3K5 or
MAP3K9
mutants in HEK293T cells reduced the phosphorylation of downstream MAP kinases. Attenuation of
MAP3K9
function in melanoma cells using siRNA led to increased cell viability after temozolomide treatment, suggesting that decreased MAP3K pathway activity can lead to chemoresistance in melanoma.
...
PMID:Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. 2219 30
