Abstract 5840: The characteristics of TP53 germline mutations analyzed in a large-scale cohort of Chinese glioma patients

Abstract

Abstract Backgrounds:TP53 germline mutation is well known to be the cause of Li-Fraumeni syndrome (LFS), a rare autosomal dominant cancer syndrome, characterized by predisposition of breast cancer, soft tissue carcinoma, osteosarcoma, brain cancer and etc. LFS has been reported in cases or small-scale cohorts for decades, while the characteristics of TP53 germline mutations carried by glioma patients were still less studied due to rarity. We performed large-scale retrospective research to identify TP53 germline mutations in Chinese glioma patients, which would extend the genetic knowledge of LFS related glioma. Methods:We enrolled 3325 glioma patients in this study (female=1423, male=1902). Next-generation sequencing panel targeting 825 genes was performed to identify TP53 germline mutations. Mutations were annotated pathogenic or likely pathogenic according to ACMG guidelines or referring to the literatures. Results:After annotation, 20 pathogenic or likely pathogenic germline mutations (PGMs) in TP53 were found in 3325 glioma patients. There was no statistical significance of gender ratio between all glioma patients and mutation carriers (female=6, male=14, p=0.25). The highest incidence rate of PGMs occurred in glioblastoma (n=16, 80.0%), followed by anaplastic astrocytoma (n=2, 10.0%), oligodendroglioma (n=1, 0.5%) and diffuse midline glioma (n=1, 0.5%). Significant difference of onset age between TP53 mutation carriers and non-carriers was pronounced (22.90YO vs 43.35YO avg, p<0.0001). Furthermore, the carrier rate of PGMs was prone to decrease with increasing onset age (table 1). Conclusions:This research indicated that TP53 PGMs were prone to occur in younger glioma patients, suggesting the importance of TP53 germline mutations being screened. It might be able to assist with early detection and treatment of glioma. The carrier rate of TP53 PGMs in each onset age intervals onset age glioma patient number PGM carrier number carrier rate 0-18 444 10 2.25% 19-30 263 4 1.52% 31-45 826 4 0.48% 46-55 717 1 0.14% 56-65 687 1 0.15% 66-75 337 0 0.00% 76+ 51 0 0.00% Citation Format: Xinyu Hong, Ximeng Zhao, Zeshang Guo, Xiaochen Yang, Bella Guo, Xiang Zhang, Tonghui Ma. The characteristics of TP53 germline mutations analyzed in a large-scale cohort of Chinese glioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5840.