Annotation Detail
Information
- Associated Genes
- TP53
- Associated Variants
-
TP53 p.Arg273His (p.R273H)
(
ENST00000510385.5,
ENST00000576024.2,
ENST00000604348.6,
ENST00000714357.1,
ENST00000269305.9,
ENST00000359597.8,
ENST00000413465.6,
ENST00000420246.6,
ENST00000445888.6,
ENST00000455263.6,
ENST00000504290.5,
ENST00000504937.5,
ENST00000714359.1,
ENST00000610292.4,
ENST00000610538.4,
ENST00000714409.1,
ENST00000610623.4,
ENST00000618944.4,
ENST00000619186.4,
ENST00000714408.1,
ENST00000619485.4,
ENST00000620739.4,
ENST00000622645.4,
ENST00000714356.1 )
TP53 p.Arg273His (p.R273H) ( ENST00000445888.6, ENST00000455263.6, ENST00000269305.9, ENST00000359597.8, ENST00000413465.6, ENST00000420246.6, ENST00000504290.5, ENST00000504937.5, ENST00000510385.5, ENST00000576024.2, ENST00000604348.6, ENST00000610292.4, ENST00000610538.4, ENST00000610623.4, ENST00000618944.4, ENST00000619186.4, ENST00000619485.4, ENST00000620739.4, ENST00000622645.4, ENST00000714356.1, ENST00000714357.1, ENST00000714359.1, ENST00000714408.1, ENST00000714409.1 ) - Associated Disease
- osteosarcoma
- Source Database
- CIViC Evidence
- Description
- Several preclinical studies were testing drug resistance mechanisms of TP53-R273H variant. Saos-2 cells were transfected with TP53-R273H mutation and these cells were used in the study. Using a western blot, Saos-2/TP53-R273H cells were shown to have a 0.6-fold down-regulation (compared to the Control) for Procaspase-3 protein expression. In addition, Saos-2/TP53-R273H cells were shown to be more resistant to methotrexate and doxorubicin. Reduced levels of drug-induced apoptosis were seen in Saos-2/TP53-R273H cells treated with doxorubicin (0.05 uM and 0.10 uM) and methotrexate (25 nM and 50 nM) in DNA fragmentation assays. According to the results, TP53-R273H induces drug resistance when procaspase-3 is down-regulated.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7430
- Gene URL
- https://civic.genome.wustl.edu/links/genes/45
- Variant URL
- https://civic.genome.wustl.edu/links/variants/122
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Osteosarcoma
- Evidence Direction
- Supports
- Drug
- Methotrexate,Doxorubicin
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 17363498
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Doxorubicin | Resitance or Non-Reponse | true |
| Methotrexate | Resitance or Non-Reponse | true |