Abstract 5875: Germline gene alterations in high grade and low grade gliomas: A multi-center, large scale study in China
Authors: Wang Jie , Guo Bella , Zhang Xiang , Zhao Ximeng , Wang Dongsheng , Sun Fei , Ma Tonghui 
Published: June 2022

Backgrounds: Germline gene alterations in gliomas play a significant role during malignant transformation of progenitor glial cells. Previous pan-caner studies suggested 6-10% of gliomas patients harboring germline gene mutations. However, these studies are limited to only known cancer predisposition genes and a small scale of gliomas patients. In this study, we performed a multi-canter, large scale study to investigate the contribution of germline gene alterations to LGG and HGG.

Methods: Genomic DNA was extracted from white blood cells from 1006 LGG patients and 1578 HGG patients and was subjected to Next-generation sequencing with Onco PanScan. Pathogenic or likely pathogenic germline variants (PGVs) were identified in 150 putative cancer-predisposition genes according to ACGM guideline. Fisher’s exact test was used for the statistics analysis (two-sided).

Results: We identified 54 PGVs in LGG patients and 112 PGVs in HGG patients which were located in 31 and 40 unique genes, respectively (Table 1). There was a significant difference between HGG and LGG in younger patients with germline gene mutations (A group, p &lt; 0.001), while not in B and C group. The results indicated that the incidence rate of TP53 or MSH2 germline mutations in HGG patients was much higher than in LGG patient (p &lt; 0.01), while a lower incidence rate of ERCC5 germline mutations was observed in HGG patients in comparison with LGG patients (p &lt; 0.05).

Conclusions: This study indicated a higher PGVs frequency in HGG than in LGG, especially in younger group. In addition, there is different contribution of germline gene alterations to risk the formation of LGG or HGG. It might aid in the early diagnosis of these patients and genetic counseling of their families.

Informations of PGVs in LGG and HGG LGG HGG Numbers of mutation carriers Numbers of LGG Mutation rate Numbers of mutation carriers Numbers of HGG Mutation rate Age A: 0-30 years 14 a*** 292 4.1% 29 b*** 189 15.3% B: 31-55 years 30 554 5.4% 41 639 6.4% C: &gt;55 years 10 160 6.3% 42 c*** 750 5.6% Total 54 1006 5.4% 112 1578 7.1% Gender Male 35 567 6.2% 65 935 7.0% Female 19 439 4.3% 50 643 7.8% Total 54 1006 5.4% 112 1578 7.1% Top ten of high mutation rate ERCC5*, MUTYH, BRCA2, CHEK2, WRN, PRSS1, MSH6, FANCD2, ERCC2, FANCA TP53**, MSH2**, BRCA2, NF1, RAD51D, MSH6, PRSS1, BUB1B, PDE11A, BLM Note: LGG 1, Low Grade Glioma; HGG 2, High Grade Glioma; aNumbers of mutation carriers in A group were statistical different in LGG and HGG patients; bNumbers of mutation carriers in A group and B group were statistical different in HGG patients; cNumbers of mutation carriers in A group and C group were statistical different in HGG patients; * p &lt; 0.05; ** p &lt; 0.01; *** p &lt; 0.001

Citation Format: Jie Wang, Bella Guo, Xiang Zhang, Ximeng Zhao, Dongsheng Wang, Fei Sun, Tonghui Ma. Germline gene alterations in high grade and low grade gliomas: A multi-center, large scale study in China [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 5875.