Combined PTEN Mutation and Protein Expression Associate with Overall and Disease-Free Survival of Glioblastoma Patients.
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor commonly inactivated in glioblastoma multiforme (GBM), but the prognostic significance of PTEN remains controversial. Here, we demon- strate significant prognostic value of combined PTEN mutation and expression for the survival of patients with GBM on the basis of analysis of large-scale cancer genomic data. PTEN nonsense mutations associated with sig- nificantly shorter disease-free survival and overexpression of PTEN protein linked to shorter disease-free and overall survival of patients with GBM. PTEN nonsense mutations correlated with decreased p53 and Gata3 protein levels and increased genomic instability in human GBM tissues. Expression of nonsense PTEN mutant decreased p53 and Gata3 levels, producing increased DNA damage both in vitro and in vivo. Mice carrying xenograft tumors with nonsense PTEN mutant displayed significantly shorter survival. Our data demonstrated the prognostic value of combined PTEN mutation and protein expression for patients with GBM and highlighted distinct biologic effects of nonsense and missense mutations of PTEN.
State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai, China. Electronic address: xujieletter@gmail.com.
Jie
J
Xu
Viral Genetics Laboratory, Vrije Universiteit Brussel, Brussels, Belgium.
Zhaoli
Z
Li
Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai, China.
Jilin
J
Wang
Shanghai Jiao Tong University School of Medicine, Renji Hospital, Shanghai, China. Electronic address: chenhaoyan@gmail.com.
Haoyan
H
Chen
Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai, China. Electronic address: fangjingyuan_new@163.com.
Jing-Yuan
JY
Fang