Annotation Detail

Information
Associated Genes
KRAS
Associated Variants
KRAS p.Gly12Val (p.G12V) ( ENST00000688940.1, ENST00000692768.1, ENST00000256078.10, ENST00000311936.8, ENST00000556131.2, ENST00000557334.6, ENST00000685328.1, ENST00000686969.1, ENST00000693229.1 )
KRAS p.Gly12Val (p.G12V) ( ENST00000693229.1, ENST00000256078.10, ENST00000311936.8, ENST00000556131.2, ENST00000557334.6, ENST00000685328.1, ENST00000686969.1, ENST00000688940.1, ENST00000692768.1 )
Associated Disease
colorectal cancer
Source Database
CIViC Evidence
Description
In 28 out of 40 (70%) metastatic colorectal cancer tumors harboring KRAS, NRAS, BRAF, or PIK3CA mutations and implanted into mice, the therapeutic combination of the MEK inhibitor AZD6244 and the PI3K/mTor inhibitor BEZ235 resulted in disease stabilization. Mean tumor growth was lower in the tumors treated with AZD6244+ BEZ235 (+77% vs. +267%, P=1E-6) compared to AZD6244 alone and (+77% vs. +222%, P=0.0014) BEZ235 alone. 32/40 tumors harbored KRAS mutations including 8 G12V mutations (3 with PIK3CA mutations) where progressive disease occurred in only 1 tumor upon doublet treatment but 6 tumors in monotherapy.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2001
Gene URL
https://civic.genome.wustl.edu/links/genes/30
Variant URL
https://civic.genome.wustl.edu/links/variants/425
Rating
3
Evidence Type
Predictive
Disease
Colorectal Cancer
Evidence Direction
Supports
Drug
Selumetinib,Dactolisib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
22392911
Drugs
Drug NameSensitivitySupported
DactolisibSensitivitytrue
SelumetinibSensitivitytrue