520P - Copy number variation spectrum analysis of primary glioblastoma

Background

Glioblastoma, IDH-wildtype (GBM) is the most common malignant tumor of the human central nervous systemwith a poor prognosis. The distribution of copy number variations and the molecular targeted therapy are unknown. Therefore, it is important to understand the somatic copy number genome profile of Chinese adult glioblastoma patients.

Methods

Next-generation sequencing of 131 genes was performed in postoperative tissues of 4294 Chinese adult glioma patients from 2019 to 2023. Standard operating procedures (SOP) were used to detect somatic mutations and copy number variations. We screened out copy number variants in glioblastoma and calculated mutation frequency and evaluated other co-mutations.

Results

Copy number variations was observed in 1871of 2839 glioblastoma samples (65.9%). The six most common genes with copy number variation were CDKN2A (48.8%), CDKN2B (47.1%), EGFR (24.3%), PTEN (17.1%), CDK4 (11.3%), PDGFRA (9.3%). Patients with EGFR amplification often carried CDKN2A (16.2%), CDKN2B (15.4) and PTEN (7.0%), while patients with PDGFRA amplification often carried KIT (7.54%), CDKN2A (6.1%) and KDR (5.9%). MDM2 (7.0%), CDKN2A (6.0%) and CDKN2B (6.2%) were common copy number variants in the CDK4-amplification group.

Conclusions

In our GBM patients, 65.9% present copy number variations RB1 cell-cycle, TP53, and RTK pathways are common signaling pathway alterations. CDKN2A/B deletion had the highest incidence and were enriched in EGFR-amplified patient. The high frequency of copy number variations in RB1 cell-cycle pathways in glioblastoma suggests that it may be a direction for targeted therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

C. Cheng.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.