Annotation Detail

Information
Associated Genes
PPP1R15A
Associated Variants
PPP1R15A p.Arg251Pro (p.R251P) ( ENST00000200453.6, ENST00000600406.2, ENST00000704026.1, ENST00000704027.1 )
PPP1R15A p.Arg251Pro (p.R251P) ( ENST00000200453.6, ENST00000600406.2, ENST00000704026.1, ENST00000704027.1 )
Associated Disease
colorectal cancer
Source Database
CIViC Evidence
Description
Exome and RNA sequencing was performed in tumor and matched normal tissue of 19 patients with metastatic colorectal cancer treated with chemotherapy and bevacizumab. The variant PPP1R15A (rs557806) showed the most significant association (P = 0.000401) with FOLFIRI-bevacizumab-driven tumor inhibition rate in exome sequencing data and the highest correlation (r = 0.74) with the drug responses in RNA sequencing data. Patients who were homozygous for the reference alleles (GG) of PPP1R15A rs557806 exhibited greater disease control rates and a tendency toward greater overall response rate than those with homozygous or heterozygous substitution alleles (GC and CC; P = 0.027 and 0.073) when treated with bevacizumab-containing regimens. PPP1R15A rs557806 nonsignificantly correlated with DCR in multivariate analysis (P = 0.054). In HCT116 xenograft tumors, tumor growth IR with FRB was 25 % in mock cells, 24 % in clones with reference alleles (G alleles) of PPP1R15A rs557806, and 17 % in clones with substitution alleles (C alleles) of PPP1R15A rs557806 (P = 0.004, day 13). FDG-PET imaging on day 7 showed FDG uptake (mean SUV max) of 0.219 and 0.500 in HCT116 xenografts expressing the reference allele (G) and substitution allele (C) of PPP1R15A rs557806, respectively (P = 0.032).
Variant Origin
Common Germline
Variant Origin
Common Germline
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1325
Gene URL
https://civic.genome.wustl.edu/links/genes/9722
Variant URL
https://civic.genome.wustl.edu/links/variants/548
Rating
1
Evidence Type
Predictive
Disease
Colorectal Cancer
Evidence Direction
Supports
Drug
FOLFIRI Regimen,Bevacizumab
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
27177629
Drugs
Drug NameSensitivitySupported
BevacizumabSensitivitytrue
FOLFIRI RegimenSensitivitytrue