Mutation causes changes in the binding domain of the enzyme.
Researchers from Eli Lilly and the Translational Genomics Research Institute (TGen) discovered a novel recurring mutation of the gene AKT1 in breast, colorectal, and ovarian cancers. AKT1 is a protein kinase that plays a key role in activating survival, proliferation, and metabolic pathways. The altered form of AKT1 appears to cause tumor cell proliferation and may play a role in making cells resistant to certain types of therapies. The findings are reported in Nature.
To identify the AKT1 mutation, the researchers analyzed 150 tumor samples from patients with either breast, colorectal, or ovarian cancer. Analysis of the data showed that 8% of breast, 6% of colorectal and 2% of ovarian tumors had the AKT1 mutation in the samples that were screened in their study.
“This discovery is a seminal finding in cancer biology that confirms AKT1 as an oncogene in breast, colorectal, and ovarian cancer. The mutation alters the electrostatics of a binding pocket in the pleckstrin homology domain, the portion of the enzyme that docks with phospholipids on the cell membrane,” says Kerry L. Blanchard, Ph.D., M.D., executive director, discovery biology research, Eli Lilly.