Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing

PTENis among the most commonly mutated tumor suppressor genesin human cancer. However, studying the role of PTENin the pathogenesis of cancer has been limited, in part, by the paucity of human cell-based isogenic systems that faithfully model PTENloss. In an effort to remedy this problem, gene editing was used to correct an endogenous mutant allele of PTENin two human glioblastoma multiforme (GBM) cell lines– 42MGBA and T98G. PTENcorrection resulted in reduced cellular proliferation that was Akt-dependent in 42MGBA cells and Akt-independent in T98G cells. This is the first report of human cancer cell lines in which mutant PTENhas been corrected by gene editing. The isogenic sets of gene edited cell lines reported here will likely prove useful for further study of PTENmutations in the pathogenesis of cancer, and for the discovery and validation of novel therapeutics targeting the PTENpathway.