Abstract 295P
Background
Gliomas are the most common and aggressive primary brain tumors in adults, with limited therapies. PIK3CA is one of the most mutated oncogenes in solid tumors. Mutations of PIK3CA are potential therapeutic targets, which has been described as early constitutive events in glioblastomas. It is thus important to understand the genomic landscape of PIK3CA in Gliomas. Here, we explored PIK3CA mutation profiles in Chinese adult glioma patients.
Methods
Next generation sequencing of 131-gene profiling was performed to analyze postoperative tissue from 1974 Chinese adult glioma patients in 2019-2021. Somatic mutations and copy number variations were detected following the standard operating procedure (SOP). We screened out PIK3CA mutation and calculated the mutation frequency, and other co-mutations were also evaluated.
Results
PIK3CA mutations were observed in 251 of 1974 tumor samples (12.7%), the average age of patients was 49.5 years (range, 19-77 years). PIK3CA mutations showed a higher frequency in the subgroup of IDH-wildtype Glioblastoma (54.1%). In oligodendrogliomas - IDH mutation and 1p/19q codeletion and IDH-mutant astrocytoma, these PIK3CA mutations were observed in 23.4% and 18.5% of cases, respectively. There was no significant statistical difference of PIK3CA mutations frequency in IDH-mutant and IDH-wildtype glioma (14.0% vs 11.9%, χ2＝1.56，P>0.05). Of 293 PIK3CA mutations, 87%(n=255) were missense mutations. Exon 2, exon21 and exon10 of PIK3CA are the main mutational hotspot regions found, with p.E542 (n=18), p.E545(n=32)，p.Q546(n=9), p.H1047(n=52) being the most frequent mutations in our study. In PIK3CA mutated patients, the ten most frequently somatic mutated genes were: TERT, TP53, IDH1, NF1, CIC, ATRX, NOTCH1, FUBP1, PTEN, SETD2.
Conclusions
In our study, PIK3CA mutations were observed in 12.7% Chinese adult glioma patients, with higher frequency in GBM molecular subgroups, and mostly occurred in exon 2, exon21 and exon10. The main mutational hotspot found: p.E542, p.E545, p.Q546, p.H1047. Therefore, targeted therapy research could be considered in the future.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.