Annotation Detail

Information
Associated Genes
MSH2
Associated Variants
MSH2 LOSS ( ENST00000233146.7 )
MSH2 LOSS ( ENST00000233146.7 )
Associated Disease
transitional cell carcinoma
Source Database
CIViC Evidence
Description
Case report of a 45-year old woman of Japanese descent with recurrent urothelial carcinoma. The patient was identified to harbor mutations in MSH2 (A913fs*2, E226*, E580*) and in MSH6 (R361H) by panel sequencing as well as loss of expression of these genes as confirmed by IHC. Testing also revealed a high mutational load as well as 2+ PD-L1 expression in 80% of the cells. The patient was treated with anti-PD-L1 inhibitor MEDI4736 and MEDI0680 in a phase 1 trial and had a complete remission within 2 months of treatment that was ongoing after 11 months.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1877
Gene URL
https://civic.genome.wustl.edu/links/genes/3628
Variant URL
https://civic.genome.wustl.edu/links/variants/808
Rating
3
Evidence Type
Predictive
Disease
Urothelial Carcinoma
Evidence Direction
Supports
Drug
Durvalumab,Anti-PD-1 Monoclonal Antibody MEDI0680
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26674132
Drugs
Drug NameSensitivitySupported
Anti-PD-1 Monoclonal Antibody MEDI0680Sensitivitytrue
DurvalumabSensitivitytrue