The landscape of EGFR mutation in Chinese patients with glioma.

e14028 Background: Epidermal growth factor receptor (EGFR), a trans-membrane receptor tyrosine kinase, consists of an extracellular ligand-binding domain (ECD), a single transmembrane domain (STMD) and an intracellular kinase domain (ICD). Glioma is the most common primary brain tumor, and variations of EGFR are frequently reported in glioma patients. This study aimed to analysis the landscape of EGFR mutation subtype in Chinese patients with glioma. Methods: We retrospectively collected 1779 patients with glioma. In all patients enrolled, the comprehensive genomic profiling containing EGFR gene was detected using tumor tissue, including WES, 539 tumor related-gene panel or 131+4 gene panel (Simceredx). And the somatic mutations including SNV, INDEL, CNV, fusion were analyzed correspondingly. Results: Among 1779 patients with glioma, EGFR mutations were identified in 392 (22.03%) patients. The age was significantly higher in patients with EGFR-mutant group than in patients without EGFR-mutant group, with median age 54 vs. 45 (p = 4.81e-19). The sex didn’t reach statistical significance in two group. The incidence rate of different EGFR mutation types among all patients with EGFR-mutant were amplification (314,80.10%), SNV(198,50.51%), Indel(24,6.12%) and fusion(44,11.22%) respectively. 162 (46.69%) had two or more mutation types simultaneously. The main partner gene of EGFR fusion was LOC100996654, followed by ELDR and SEC61G, and the main EGFR breakpoints were in intron24, intron7, exon7. Within 347 SNV and Indel mutations, exon7, 15, 20, 6 and 8 were detected in 103(29.68%), 50(14.41%), 28 (8.07%), 25(7.20%) and 18 (5.19%) respectively. The top three mutaton subtypes within exon7 were account for 19.31%, which included p.A289V,p.A289T,p.T263P. Meanwhile, the mutation frequency within ICD encoded by exons 18-24 was 17.00%, in which exon20 mostly distributed (8%). In exon20, the most common mutation subtypes were p.V774M,p.H773dup,p.T790M, while in the second proportion exon18 (3.46%), the main subtype were p.G719A/D. Conclusions: EGFR amplification was the most common mutation type. There were 122 SNV and Indel subtypes altogether and occurred throughout almost the entire exon region, in which exon7 contained maximum 21 different subtypes and the p.A289V was the main type. The distribution of subtypes in ECD were much more than in ICD. The relationship between subtypes occurrence and cancer will be further studied in the future.