Annotation Detail

Information
Associated Genes
FGFR1
Associated Variants
FGFR1 p.Asn542Lys (p.N542K) ( ENST00000326324.10, ENST00000335922.9, ENST00000341462.9, ENST00000356207.9, ENST00000397091.9, ENST00000397103.5, ENST00000397108.8, ENST00000532791.5, ENST00000397113.6, ENST00000425967.8, ENST00000447712.7, ENST00000683765.1, ENST00000683815.1, ENST00000684654.1, ENST00000703405.1 )
FGFR1 p.Asn542Lys (p.N542K) ( ENST00000326324.10, ENST00000683815.1, ENST00000684654.1, ENST00000703405.1, ENST00000532791.5, ENST00000335922.9, ENST00000341462.9, ENST00000356207.9, ENST00000397091.9, ENST00000397103.5, ENST00000397108.8, ENST00000397113.6, ENST00000425967.8, ENST00000447712.7, ENST00000683765.1 )
Associated Disease
Ewing sarcoma of bone
Source Database
CIViC Evidence
Description
116 Ewing's sarcoma tumor samples were analyzed in this study. 2 patient's samples underwent whole genome sequencing, tumor samples from 51 patients underwent exome sequencing and expression analysis, 63 samples underwent FGFR1 copy number analysis, mRNA analysis and IHC. A FGFR1 N546K mutation was detected in one patient. Gain of the FGFR1 locus (qPCR) was observed in 13 of 41 patients (31.7%) and Ewing sarcoma cell lines (A673, CADO, SK-NMC, SK-ES, and VH-64). FGFR1 was also highly expressed in Ewing sarcoma (mRNA and IHC) and correlated with copy number. Retroviral transduction of FGFR1 wild-type or the FGFR1 N546K mutant into NIH3T3 cells led to enhanced proliferation especially for cells harboring the FGFR1 mutation. ShRNA mediated knockdown of FGFR1 inhibited growth of Ewing sarcoma and other cancer cells (A549 lung carcinoma cell line or leukemia cell lines HL60 and Kasumi) with almost complete growth suppression only in the Ewing sarcoma cell lines and knockdown of FGFR1 abrogated growth of cell lines in xenograft. Ponatinib treatment inhibited growth of Ewing sarcoma cell lines.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1246
Gene URL
https://civic.genome.wustl.edu/links/genes/1885
Variant URL
https://civic.genome.wustl.edu/links/variants/515
Rating
2
Evidence Type
Predictive
Disease
Ewing Sarcoma Of Bone
Evidence Direction
Supports
Drug
Ponatinib
Evidence Level
E
Clinical Significance
Sensitivity/Response
Pubmed
26179511
Drugs
Drug NameSensitivitySupported
PonatinibSensitivitytrue