Mutational analysis of AKT1, AKT2 and AKT3 genes in common human carcinomas.
OBJECTIVE
Mounting evidence indicates that alterations in AKT proteins play an important role in the pathogenesis of cancer. The objective of this study was to see whether common human carcinomas harbor AKT mutations that might contribute to the development of cancer.


METHODS
We performed mutational analysis of the kinase domains of AKT1-AKT3 by a single-strand conformation polymorphism assay in 294 carcinoma tissues from the stomach, lung, colon and breast.


RESULTS
Overall, we detected three somatic mutations in AKT2, but no mutations in AKT1 or AKT3 in the 294 cancer tissues. The AKT2 mutations were detected in 1 of 51 gastric carcinomas (2.0%) and 2 of 79 lung carcinomas (2.5%). AKT2 mutations consisted of one missense mutation and 2 splice site mutations in the intron. We simultaneously analyzed somatic mutations in EGFR, ERBB2, K-RAS, PIK3CA and BRAF genes in the 3 samples with the AKT2 mutations, and found a lung adenocarcinoma with the AKT2 missense mutation harbored an EGFR mutation.


CONCLUSIONS
This study demonstrated that somatic mutations in the kinase domain of AKT2 occur in a small fraction of common human cancers, and suggested that alterations in the AKT2-mediated signaling pathway by AKT2 mutation could contribute to the development of some cases of human cancers.
Soung
Young Hwa
YH
Department of Pathology, College of Medicine, Catholic University of Korea, Banpo-Dong, Socho-Gu, Seoul, Korea.
Lee
Jong Woo
JW
Nam
Suk Woo
SW
Lee
Jung Young
JY
Yoo
Nam Jin
NJ
Lee
Sug Hyung
SH
D002277:Carcinoma / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D018807:Polymorphism, Single-Stranded Conformational; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
D004273:DNA, Neoplasm; C494918:AKT1 protein, human; C494921:AKT2 protein, human; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt