Annotation Detail
Information
- Associated Genes
- AKT1
- Associated Variants
-
AKT1 p.Gln79Lys (p.Q79K)
(
ENST00000554192.6,
ENST00000554581.5,
ENST00000402615.6,
ENST00000554848.5,
ENST00000555458.6,
ENST00000407796.7,
ENST00000349310.7,
ENST00000553797.2,
ENST00000555528.5,
ENST00000649815.2,
ENST00000683722.1,
ENST00000714123.1,
ENST00000714130.1 )
AKT1 p.Gln79Lys (p.Q79K) ( ENST00000349310.7, ENST00000402615.6, ENST00000407796.7, ENST00000553797.2, ENST00000554192.6, ENST00000554581.5, ENST00000554848.5, ENST00000555458.6, ENST00000555528.5, ENST00000649815.2, ENST00000683722.1, ENST00000714123.1, ENST00000714130.1 ) - Associated Disease
- melanoma
- Source Database
- CIViC Evidence
- Description
- In a retrospective study of 44 relapsed melanoma patients with BRAF V600E/K (known BRAF inhibitor sensitizing mutations), AKT1 Q79K was associated with acquired resistance to BRAF inhibitor (dabrafenib) monotherapy in one patient. This patient was a 38 year old female with stage IV M1a melanoma who took dabrafenib (35 mg twice daily to 100 mg three times a day). The best overall response was a 100% reduction in the sum of target lesions, and progression free survival lasted 119 days. Prior to dabrafenib monotherapy, this patient's baseline tumor harbored BRAF V600K—no other somatic alterations were noted. Following relapse, the patient gained AKT1 Q79K in one of two disease progressive tumors. Whole exome sequencing and Sanger re-sequencing were used for all tumors. The authors hypothesized that disruptions in the PI3K-PTEN-AKT pathway represent a core mechanism of acquired resistance to BRAF inhibitor therapy.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/6260
- Gene URL
- https://civic.genome.wustl.edu/links/genes/2
- Variant URL
- https://civic.genome.wustl.edu/links/variants/169
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Melanoma
- Evidence Direction
- Supports
- Drug
- Dabrafenib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 24265155
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Dabrafenib | Resitance or Non-Reponse | true |