AKT1 pleckstrin homology domain E17K activating mutation in endometrial carcinoma.
OBJECTIVE
The PI3K/AKT pathway is frequently activated in endometrial carcinoma (EC) mainly due to mutations in the PIK3CA and PTEN genes. These events are common and believed to be the key to endometrial carcinogenesis. Recently, a somatic activating mutation in the AKT1 gene (E17K) was identified in several cancer types. In this study we explored the frequency of this AKT1 mutation in endometrial carcinoma.


METHODS
Tumor DNA, extracted from 73 EC was analyzed for AKT1 E17K mutation (G49A) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In addition, the tumors were screened for coexisting common mutations in PTEN, PIK3CA and KRAS.


RESULTS
The AKT1 E17K mutation was detected in 4% of EC. One of the AKT1-mutated tumors showed coexisting PTEN loss-of-function mutation.


CONCLUSIONS
We identified the AKT1 E17K mutation in 4% of endometrial carcinomas. The presence of double AKT1/ PTEN mutants is in accord with the hypothesis that in EC more than one hit is required to completely activate the PI3K pathway. Furthermore, AKT1 mutations were limited to high grade, advanced stage tumors suggesting that this mutation confers a more aggressive tumor behavior.
Cohen
Yoram
Y
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Israel. ycohen1@gmail.com
Shalmon
Bruria
B
Korach
Jacob
J
Barshack
Iris
I
Fridman
Eddie
E
Rechavi
Gideon
G
D000368:Aged; D001798:Blood Proteins / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001798:Blood Proteins; D004273:DNA, Neoplasm; D010750:Phosphoproteins; C039077:platelet protein P47; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human