Annotation Detail

Information
Associated Genes
MAP2K1
Associated Variants
MAP2K1 p.Lys57Asn (p.K57N) ( ENST00000686347.1, ENST00000693150.1, ENST00000307102.10, ENST00000692683.1, ENST00000685763.1, ENST00000685172.1, ENST00000691576.1, ENST00000691937.1, ENST00000689951.1 )
MAP2K1 p.Lys57Asn (p.K57N) ( ENST00000307102.10, ENST00000685172.1, ENST00000685763.1, ENST00000686347.1, ENST00000689951.1, ENST00000691576.1, ENST00000691937.1, ENST00000692683.1, ENST00000693150.1 )
Associated Disease
lung adenocarcinoma
Source Database
CIViC Evidence
Description
Mutational profiling of a large cohort of lung adenocarcinomas identified in 2 of 207 primary lung tumors a somatic activating mutation in exon 2 of MEK1 (i.e., mitogen-activated protein kinase kinase 1 or MAP2K1) that substitutes asparagine for lysine at amino acid 57 (K57N) in the nonkinase portion of the kinase. Neither of these two tumors harbored known mutations in other genes encoding components of the EGFR signaling pathway (i.e., EGFR, HER2, KRAS, PIK3CA, and BRAF). Expression of mutant, but not wild-type, MEK1 leads to constitutive activity of extracellular signal-regulated kinase (ERK)-1/2 in human 293T cells and to growth factor-independent proliferation of murine Ba/F3 cells. A selective MEK inhibitor, AZD6244, inhibits mutant-induced ERK activity in 293T cells and growth of mutant-bearing Ba/F3 cells.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2936
Gene URL
https://civic.genome.wustl.edu/links/genes/31
Variant URL
https://civic.genome.wustl.edu/links/variants/1272
Rating
2
Evidence Type
Predictive
Disease
Lung Adenocarcinoma
Evidence Direction
Supports
Drug
Selumetinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
18632602
Drugs
Drug NameSensitivitySupported
SelumetinibSensitivitytrue