Annotation Detail

Information
Associated Genes
MAP2K1
Associated Variants
MAP2K1 p.Gln56_Val60del (p.Q56_V60del) ( ENST00000685172.1, ENST00000692683.1, ENST00000685763.1, ENST00000693150.1, ENST00000307102.10, ENST00000689951.1, ENST00000691937.1, ENST00000686347.1, ENST00000691576.1 )
MAP2K1 p.Gln56_Val60del (p.Q56_V60del) ( ENST00000307102.10, ENST00000685172.1, ENST00000685763.1, ENST00000686347.1, ENST00000689951.1, ENST00000691576.1, ENST00000691937.1, ENST00000692683.1, ENST00000693150.1 )
Associated Disease
ovarian serous carcinoma
Source Database
CIViC Evidence
Description
Case report of a 51-year old patient with recurrent low-grade serous ovarian cancer. Selumetinib treatment in a phase-II trial led to a complete and durable response > 5 years. Sequencing (MSK-IMPACT Panel) was performed on the patients tumor and germline and identified a 15-bp in-frame deletion of MAP2K1 (8.3% of tumor reads but 0% in germline). In-silico modelling suggested loss of negative feedback on kinase activity from this deletion.In-vitro expression of the MEK1 Q56_V60 deletion as well as the previously characterized MEK1 F53L mutation in 293H cells resulted in elevated levels of phosphorylated ERK and phosphorylated ribosomal protein S6 kinase as compared with wild-type MEK1 as well as increased colony formation and tumor growth in-vivo. Selumetinib treatment of MEK1-transfected cells confirmed retained sensitivity to MEK inhibition and inhibition of colony formation.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1661
Gene URL
https://civic.genome.wustl.edu/links/genes/31
Variant URL
https://civic.genome.wustl.edu/links/variants/655
Rating
4
Evidence Type
Predictive
Disease
Ovarian Serous Carcinoma
Evidence Direction
Supports
Drug
Selumetinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26324360
Drugs
Drug NameSensitivitySupported
SelumetinibSensitivitytrue