Abstract 806P
Background
Sarcoma are very rare in uterine tumors, and the clinical treatment is limited. The purpose was to study the gene variation characteristics and potential drug targets of uterine sarcoma.
Methods
24 cases with uterine sarcoma were collected, including 9 leiomyosarcoma cases, 9 endometrial stromal sarcomas (ESS), 5 carcinosarcomas and 1 rhabdomyosarcoma (RMS). Targeted next generation sequencing (NGS) of 450 genes was performed in a CAP/CLIA certified OrigiMed laboratory (Shanghai, China). Genomic alterations, tumor mutational burden (TMB), PD-L1 expression, potential target drugs and immune checkpoint inhibitors (ICIs) were assessed.
Results
The median age of all enrolls was 37 years old（min-max:19-68), which was younger than the mean age of onset (>50 years) and median age (60-65 years) of uterine tumors. Among the 24 enrolled patients, 17 patients have at least one potential target mutation and/or ICIs effective marker according to the test results. That was to say, 70.83% (17/24) patients may benefit from target therapy or immunotherapy. 5 patients with CDK4, CDKN2A or CDKN2B mutations were recommended with CDK4/6 inhibitors, 4 patients with TSC2, FBXW7 or PTEN mutations were recommended with PI3K/mTOR inhibitors, 3 patients with FGFR1, FGFR2 or FGFR3 amplifications were recommended with FGFR inhibitors, 2 patients with BRCA or ATM mutations were recommended with PAPR inhibitors, 2 patients with NTRK1 or NTRK3 fusions were recommended with larotrectinib, etc. In addition, 5 patients were recommended with ICIs. High frequency mutation genes vary greatly among uterus leiomyosarcoma, ESS and carcinosarcomas. The top 5 mutated genes of leiomyosarcoma were TP53 (66.67%), ATRX (44.44%), RB1 (44.44%), BRCA2 (33.33%) and MED12 (33.33 %). ESS had less gene variations, and the highest frequency mutated genes was 22.22% (2/9), including ATRX, CCND2, CDKN1B, CDKN2A, CDKN2B, etc. TP53 (100%), LRP1B (60%) and PTEN (60%) were the top 3 mutated genes in carcinosarcomas, followed with AR (40%), FBXW7 (40%) and FGFR1 (40%). Finally, carcinosarcomas had a higher TMB values than leiomyosarcoma and ESS (P=0.038).
Conclusions
Our study firstly revealed the characteristics of gene variation and potential target drugs/ICIs in Chinese patients with uterine sarcoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.