Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma.

摘要: PTEN is one of the most frequently altered tumor suppressor genes in malignant tumors. The dominant-negative effect alteration suggests that aberrant function mutation might be more disastrous than deletion, frequent genomic event glioblastoma (GBM). This study aimed to understand functional properties various missense mutations and investigate their clinical relevance. landscape was analyzed using Samsung Medical Center GBM cohort validated via Cancer Genome Atlas dataset. Several hotspot were identified, subcellular distributions phenotypes evaluated. We established a library cancer cell lines overexpress these mutant proteins U87MG patient-derived models lacking PTEN. categorized into two major subsets: phosphatase domain truncal C2 domain. determined compartmentalization four (H93Y, C124S, R130Q, R173C) from former group found they had distinct localizations; those associated with invasive (‘edge mutations’) localized periphery, while R173C nucleus. Invasive derived edge substitutions unaffected by an anti-PI3K/Akt agent but disrupted microtubule inhibitors. exhibit regarding localization. Further, some caused enhanced invasiveness dysfunctional cytoskeletal assembly, thus suggesting it potent therapeutic target.