Genomic profiling of Chinese patients with endometrial adenocarcinoma (EA).

person Guo Huiming The First Affiliated Hospital of Kunming Medical University, Kunming, China info_outline Guo Huiming, Jin Yuni, Su Liangdi, Liu Yuan, Bao Chan, Li Tian, Zhang Juan, Bei Zhang

Authors person Guo Huiming The First Affiliated Hospital of Kunming Medical University, Kunming, China info_outline Guo Huiming, Jin Yuni, Su Liangdi, Liu Yuan, Bao Chan, Li Tian, Zhang Juan, Bei Zhang Organizations The First Affiliated Hospital of Kunming Medical University, Kunming, China, Medical Affairs, 3D Medicines, Shanghai, China Abstract Disclosures Research Funding No funding sources reported Background: Incidences of endometrial adenocarcinoma are increasing in the Chinese with poor prognosis. Our aim was to explore the genomic profiling of Chinese endometrial adenocarcinoma and whether they could provide potential prognostic and therapeutic implications. Methods: Between January 2019 and August 2023, a total of 204 samples, were obtained from Chinese EA patients at the 3DMed Biobank (Shanghai, China) and The First Affiliated Hospital of Kunming Medical University. Genomic alterations were determined using NGS 733 cancer-related genes panel. TMB-H was defined as above 10 mutation/Mb. Positive PD-L1 expression was defined as ≥1 of CPS. Statistical analyses were performed using R version 3.4.4. Results: A total of 204 patients with EA were included in this study. The median age at diagnosis was 56 (range, 27-92) years old. Among these 204 tissue samples, 178 (87%) were collected from primary lesions. 9.0 %( 12/133) patients exhibited positive PD-L1 CPS status. 19.6% of patients in our cohort exhibited MSI. Median TMB was 6.15 mutation/Mb [0, 473], and 33.8% patients had TMB-H status. In this cohort, a total of 9404 somatic alterations were detected in 96.1% of the patients (196/204), with an average of 46 alterations per patient. The most commonly alternated genes were PTEN (68%), ARID1A (50%), PIK3CA (47%), PIK3R1 (32%), TP53 (31%), ZFHX3 (30%), CTCF (25%), KMT2C (23%), KRAS (22%), CTNNB1 (22%), CHD4 (18%), FAT4 (18%), FAT1 (18%), NCOR2 (17%), ARID1B (17%), AR (16%), BCOR1 (16%), MYC (16%), and NF1 (16%). The hotspot mutations (prevalence higher than 2%) in Chinese EA included PTEN p. R130G, PIK3CA p.R88Q, RNF43 p.G659Vfs*41, PIK3CA p.H1047R, KMT2C p.K2797Rfs*26, CTCF p.T204Nfs*26, KRAS p.G12D, and TEAD2 p.H295Mfs*12. In terms of structural-rearrangements, ten fusions were detected in six genes, with NOTCH2 (n = 4) and RAF1 (n = 2) having the highest number of events. In terms of CNVs, frequently affected genes in Chinese EA included PTEN (249), ARID1A (172), PIK3CA (137), ZFHX3 (110), LRP1B (96), and FAT4 (93). The frequently affected pathways were PI3K (88%), RTK-RAS (72%), and WNT (54%) Furthermore, pathogenic or likely pathogenic germline variants were observed in 33 patients (16.2%). The affected genes included MSH6 (6), MLH1 (4), MSH2 (4), ATM (3), FANCA (3), BRCA2 (3), BRCA1 (2), PMS2 (2), APC (1), BARD1 (1), BLM (1), CDH1 (1), FANCD2 (1), FANCG (1), PALB2 (1), RAD50 (1), RAD54L (1), and RECQL4 (1). Conclusions: In summary, we presented the large-scale genomic profiling of EA in the Chinese population and demonstrated emphasizes the importance of molecular characterization in facilitating clinical decision-making and improving patient outcomes in EA.

Pre-clinical