Annotation Detail

Information
Associated Genes
NRG1
Associated Variants
NRG1 ATP1B1-NRG1 fusion
Associated Disease
pancreatic ductal adenocarcinoma
Source Database
CIViC Evidence
Description
Whole genome sequencing and transcriptomic analysis were performed on 47 advanced PDAC patients. 3/47 patients were KRAS wildtype and all three of these cases harbored a NRG1 fusion. A 59-year-old metastatic PDAC patient harbored an in-frame fusion of exon 3 of ATP1B1 with exon 2 of NRG1 and no other observed clinically relevant small mutations. Compared to this PDAC cohort, significant overexpression of NRG1 (exons 2-7) was observed in the tumor. Of note, the EGF-like domain of NRG1 (exons 6 & 7), which is required for HER-family kinase activation, is preserved in the fusion. Treatment with afatinib resulted in significant clinical response as measured by imaging, as well as a drastic reduction in CA19-9 levels. Disease progression was noted 5.5 months after treatment initiation.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7492
Gene URL
https://civic.genome.wustl.edu/links/genes/2593
Variant URL
https://civic.genome.wustl.edu/links/variants/2178
Rating
3
Evidence Type
Predictive
Disease
Pancreatic Ductal Adenocarcinoma
Evidence Direction
Supports
Drug
Afatinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
31068372
Drugs
Drug NameSensitivitySupported
AfatinibSensitivitytrue