Annotation Detail

Information
Associated Genes
KRAS
Associated Variants
KRAS p.Gly12Cys (p.G12C) ( ENST00000256078.10, ENST00000311936.8, ENST00000556131.2, ENST00000557334.6, ENST00000685328.1, ENST00000686969.1, ENST00000688940.1, ENST00000692768.1, ENST00000693229.1 )
KRAS p.Gly12Cys (p.G12C) ( ENST00000256078.10, ENST00000311936.8, ENST00000556131.2, ENST00000557334.6, ENST00000685328.1, ENST00000686969.1, ENST00000688940.1, ENST00000692768.1, ENST00000693229.1 )
Associated Disease
colorectal cancer
Source Database
CIViC Evidence
Description
In a study of 448 metastatic colorectal cancer patients treated with EGFR-TKIs and tested for EGFR and KRAS mutations, 69 tested positive for KRAS mutations. In 38 EGFR wildtype patients treated with erlotinib or gefitinib, those with KRAS G12C mutations (n=24) had shorter progression free survival rates compared to patients with non-G12C KRAS mutations (n=14; 4.3 vs 9 weeks; P = 0.009; HR=2.7). This was true when restricted to patients with an adenocarcinoma subtype only (n=18 vs 12; 4.1 vs 9 weeks; P = 0.007; HR=3.1). Overall survival was not different between groups.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1216
Gene URL
https://civic.genome.wustl.edu/links/genes/30
Variant URL
https://civic.genome.wustl.edu/links/variants/78
Rating
3
Evidence Type
Predictive
Disease
Colorectal Cancer
Evidence Direction
Supports
Drug
Gefitinib,Erlotinib
Evidence Level
B
Clinical Significance
Resistance
Pubmed
23313110
Drugs
Drug NameSensitivitySupported
ErlotinibResitance or Non-Reponsetrue
GefitinibResitance or Non-Reponsetrue