Abstract 367P
Background
Gliomas are the most frequently occurring primary tumor of the central nervous system, of which HGG is an aggressive form with no effective therapy. So far, standard therapy in the adult setting includes maximal safe surgical resection followed by adjuvant temozolomide and radiation therapy (RT). Stromal Antigen-2 (STAG2) is a component of the cohesion complex that is required for DNA replication, the cohesion of the sister chromatids, and transcriptional regulation. Inactivating mutations in STAG2 can lead to aneuploidy and chromosomal instability in cancer. Within glioblastoma, approximately 4-6% of tumors harbor STAG2 mutations, according to large-scale genomic databases. At present, cell line trials have reported that glioblastomas carrying STAG2 mutations are sensitive to PARP inhibitors. To explore the possibility of more targeted drugs in glioma, herein, we explore STAG2 mutation profiles in Chinese adult gliomas.
Methods
Tumor specimens from 915 Chinese clinical glioma patients were analyzed using the 131-gene profiling, including all the exons of the STAG2 gene, flanking intronic regions. STAG2 mutations were detected by following the standard operating procedure (SOP).
Results
A total of 67 STAG2 aberrations, including mutations, amplification, and deletion were detected in 50/915 adult glioma patients. Loss of function (LOF) mutations, including frameshift, nonsense, splicing was more (43/67, 71.6%) observed, and 26.9% are missense mutations. STAG2 mutations were more frequently observed in IDH wild-type glioma (7.3%, 43/590) than IDH mutation glioma (2.15%, 7/325). There was a significant difference in the frequency of IDH wild-type and IDH-mutant gliomas with STAG2 mutations (7.3% vs. 2.15%, P=0.001217). 36/43 cases of clinical staging are grade IV and others are unknown. Pathway enrichment analysis was performed, and both GO and KEGG enrichment revealed no significant differences in the functions or biological processes between STAG2 mutation and wild type.
Conclusions
In our Chinese patients, STAG2 gene mutations mostly occur in IDH wild-type gliomas and may be a molecular marker of IDH wild-type glioma. PARP inhibitors may be a potential treatment option for IDH wild-type gliomas accompanying STAG2 mutation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Y. Bo.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.