Annotation Detail

Information
Associated Genes
PTEN
Associated Variants
PTEN p.Thr319Ter (p.T319*) ( ENST00000713839.1, ENST00000371953.8, ENST00000472832.3, ENST00000688308.1, ENST00000700021.1, ENST00000700029.2 )
PTEN p.Thr319Ter (p.T319*) ( ENST00000371953.8, ENST00000472832.3, ENST00000688308.1, ENST00000700021.1, ENST00000700029.2, ENST00000713839.1 )
Associated Disease
skin melanoma
Source Database
CIViC Evidence
Description
A 26-year old patient presented with vemurafenib resistant BRAF V600E-mutated cutaneous melanoma. Five metastases were evaluated using whole genome sequencing and a 4-bp deletion in PTEN (frameshift mutation at V317) was identified as unanimously present in all five tumors and a pre-treatment biopsy. The other copy of PTEN was lost with a chromosome-wide loss of chr 10. Subsequently, a patient-derived tumor cell line (designated 22 092) was suspended in a solution of PD184352/MK2206 combination therapy and cell growth inhibition confirmed tumor sensitivity to MEK/AKT inhibitors compared to the BRAF V600E-containing A375P cell line. ERK inhibitor resistance was demonstrated as a result of a GNAQ Q209P mutation also identified in the patient. This cell line showed overexpression of AKT and no expression of PTEN.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1534
Gene URL
https://civic.genome.wustl.edu/links/genes/41
Variant URL
https://civic.genome.wustl.edu/links/variants/605
Rating
3
Evidence Type
Predictive
Disease
Skin Melanoma
Evidence Direction
Supports
Drug
MEK Inhibitor CI-1040,Akt Inhibitor MK2206
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
24504448
Drugs
Drug NameSensitivitySupported
Akt Inhibitor MK2206Sensitivitytrue
MEK Inhibitor CI-1040Sensitivitytrue