The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas.
BACKGROUND
The phosphatidylinositol 3'-kinase (PI3K)-AKT pathway is activated in many human cancers and plays a key role in cell proliferation and survival. A mutation (E17K) in the pleckstrin homology domain of the AKT1 results in constitutive AKT1 activation by means of localisation to the plasma membrane. The AKT1 (E17K) mutation has been reported in some tumour types (breast, colorectal, ovarian and lung cancers), and it is of interest which tumour types other than those possess the E17K mutation.


METHODS
We analysed the presence of the AKT1 (E17K) mutation in 89 endometrial cancer tissue specimens and in 12 endometrial cancer cell lines by PCR and direct sequencing.


RESULTS
We detected two AKT1 (E17K) mutations in the tissue samples (2 out of 89) and no mutations in the cell lines. These two AKT1 mutant tumours do not possess any mutations in PIK3CA, PTEN and K-Ras.


CONCLUSIONS
Our results and earlier reports suggest that AKT1 mutations might be mutually exclusive with other PI3K-AKT-activating alterations, although PIK3CA mutations frequently coexist with other alterations (such as HER2, K-Ras and PTEN) in several types of tumours.
Shoji
K
K
Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Oda
K
K
Nakagawa
S
S
Hosokawa
S
S
Nagae
G
G
Uehara
Y
Y
Sone
K
K
Miyamoto
Y
Y
Hiraike
H
H
Hiraike-Wada
O
O
Nei
T
T
Kawana
K
K
Kuramoto
H
H
Aburatani
H
H
Yano
T
T
Taketani
Y
Y
D001798:Blood Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism
D001798:Blood Proteins; D010750:Phosphoproteins; C039077:platelet protein P47; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human