LAUSR

Abstract Background Endometrial cancer (EC) is one of the most common gynaecological tumours. Tumour mutational burden (TMB) has emerged as a promising predictor to evaluate efficacy to immunotherapy in several kinds of solid tumours. However, the relationship between TMB and genetic features of EC remains unclear. Methods Total 50 EC patients including 41 endometrioid adenocarcinoma, 6 uterine serous adenocarcinoma, 1 uterine clear cell carcinoma, 1 endometrial squamous cell carcinoma and 1 endometrial adenosquamous carcinoma were enrolled in this study. The ECs had been classified as FIGO I (n = 14), II (n = 6), III (n = 12), IV (n = 16) and not available (n = 2). FFPE tumour and matched blood samples were collected from patients for NGS-based targeted panel sequencing (450 genes). Genomic alterations and TMB were assessed. Results The 50 patients had a median age of 56 years (range, 32-73 years) with a median TMB of 3.8 muts/Mb (interquartile range (IQR), 1.5-13.7 muts/Mb). We found recurrent mutations, including PTEN (64%), PIK3CA (44%), ARID1A (40%), PIK3R1 (36%), TP53 (32%), CHD4 (20%), and KRAS (20%). FGFR2 mutations were occurred in 7 (14%) patients. The most frequently mutated genes in early-stage (FIGO I and II) were PTEN (85%), ARID1A (50%), PIK3R1 (50%), PIK3CA (40%), LRP1B (30%), and CHD4 (30%), while the most common mutations in advanced-stage (FIGO III and IV) were PTEN (46%), PIK3CA (43%), TP53 (43%), ARID1A (36%), PIK3R1 (29%), and KRAS (21%). We also found that all POLE mutations (5/5) occurred in early-stage. Mutations of PIK3R1, CHD4, CTCF, SETD2, PPP2R1A, NF1, BRCA2, ARID1B and POLE were associated with TMB-high (TMB-H, TMB≥10muts/Mb) (P  100 muts/Mb). At least one actionable mutation was identified in 86% (43/50) patients. Conclusions PI3K signaling pathway genes, PTEN, PIK3CA and PIK3R1 were most frequently mutated in EC. 26% patients (13/50) had TMB-H. POLE mutations likely occurred in early stage and were related with TMB-H, which may provide potential targets for immunotherapy of EC. Legal entity responsible for the study The authors. Funding National Natural Science Foundation of China (Youth fund project, no. 81602267). Disclosure Y. Zhang: Full / Part-time employment: OrigiMed. S. Zhang: Full / Part-time employment: OrigiMed. S. Zhao: Full / Part-time employment: OrigiMed. F. Guo: Full / Part-time employment: OrigiMed. F. Pang: Full / Part-time employment: OrigiMed. L. Zhang: Full / Part-time employment: OrigiMed. X. Dong: Full / Part-time employment: OrigiMed. K. Wang: Full / Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.