LAUSR

e23532 Background: Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. The clinical presentation and gene mutations in different subtypes are often atypical, and the profile of gene mutations vary widely. Meanwhile there are many genetic mutations difference between West countries patients and Chinese patients in many cancer types, however little is known about soft tissue tumors' difference. Methods: Next-generation sequencing data and clinical data were collected from 255 Western soft-tissue sarcoma patients (TCGA cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 271 Chinese soft-tissue sarcoma patients (Chinese cohort). Both somatic mutations and germline mutations were detected on the Chinese cohort, then we compared the somatic mutations between TCGA and Chinese cohort. Results: In Chinese cohort, top 5 mutant genes were TP53(35.69%), ATRX(14.12%), MUC16(12.94%), RB1(10.98%), CSMD1(8.24%); while in TCGA cohort were TP53(22.88%), MUC16(8.12%), RB1(6.27%), TERT(5.17%), NF1(4.80%). The mutation frequency of 7 genes were higher in TCGA cohort than in Chinese cohort: TP53(35.69% vs 22.88%, p = 0.0015), ATRX(14.12% vs 4.06%, p < 0.001), CSMD1(8.24% vs 1.85%, p < 0.001), LRP1B(6.27% vs 2.21%, p < 0.05), CSMD3(3.92% vs 1.11%, p < 0.05), EPHA7(3.92% vs 0.74%, p < 0.05) and PIK3C2G(3.53% vs 0.37%, p = 0.009). However, TERT showed the opposite, which in TCGA cohort(1.57%) was lower than Chinese cohort(5.17%)(p < 0.05). Meanwhile, we detected the germline mutations in Chinese cohort. There are three patients had BRCA1 mutations, the SLX4, TP53, MUTYH, ATM, ERCC3 and NBN were all only happened once. There were 21 patients from Chinese cohort had EWSR1-X fusions, including EWSR1-ERG(6/21, 28%), EWSR1-FLI1(6/21,28%), EWSR1-ATF1(4/21,19%), EWSR1-CREB1(1/21,5%), EWSR1-DCTN2 (1/21, 5%), EWSR1-POU5F1(1/21, 5%), EWSR1-WT1(1/21, 5%).Besides, we discovered a novel fusion gene EWSR1-DDIT3(1/21, 5%) in Chinese cohort. Conclusions: We described the general landscape and differences of genetic variation in Chinese and Western populations, we also discovered some new mutations such as novel fusion.In conclusion, comprehensive genomic profiling in a large cohort highlights the promise of targeted therapies.