Abstract 1653P
Background
Sarcomas are malignant neoplasms with low prevalence, but with high heterogeneity. So far, more than 50 distinct subtypes of sarcoma have been identified. The genomic features of sarcomas need more exploration with the aim of guiding targeted therapy and immunotherapy.
Methods
Either tissue or blood were collected from 610 sarcoma patients to perform next generation sequencing (NGS). Validated commercial panels containing more than 150 genes were used. Microsatellite instability (MSI) status was identified using the commercial panels containing MSI 100 loci. Tumour mutation burden (TMB) was calculated according to NGS results obtained from the panels with panel size≥ 0.5MB.
Results
In total, 406 sarcoma patients from 23 distinct subtypes were sequenced and 204 patients were diagnosed without subtype. The median age of the patients was 52 [1, 90]. The top five incident subtypes were liposarcoma (63, 10.33%), leiomyosarcoma (54, 8.85%), osteosarcoma (40, 6.56%), rhabdomyosarcoma (29, 4.75%) and fibrosarcoma (25, 4.10%). On average, 4.5 mutations per tissue sample and 3.1 per ctDNA sample were identified as pathogenic (MUT) or likely pathogenic mutation (VLM) (Tabel 1). The frequency of mutated genes was studied in each subtype. Since the expression of MDM2 and CDK4 are diagnostic markers for liposarcoma, the frequency of MDM2 MUT and CDK4 MUT was high (>60%) in liposarcoma, as well as in osteosarcoma (>10%) and rhabdomyosarcoma (>10%). Meanwhile, MDM2 amplification was reported to be corelated to immunotherapy hyperprogression in several solid tumour cases, revealing poor response to PD-1/ PD-L1 antibody. As a response predictor, MSI status was detected in 504 patients, among which there were 3 MSI-H. The median TMB was 3.22 [0, 91.93] Table: 1653P
| Total variances | Tissue sample (n= 548) | ctDNA sample (n= 62) | ||
| 9414 | 475 | |||
| Somatic MUT/VLM | 1894 | 20.12% | 1894 | 20.12% |
| SNV | 576 | 6.12% | 576 | 6.12% |
| CNV | 1279 | 13.59% | 1279 | 13.59% |
| fusion | 39 | 0.41% | 39 | 0.41% |
| Germline MUT/VLM | 564 | 5.99% | 564 | 5.99% |
| Total variant of uncertain significance (VOUS) | 3159 | 33.56% | 3159 | 33.56% |
Conclusions
In this study, the incidence of positive biomarkers for immunotherapy in sarcoma patients was low. With the aim of enlarging the number of patients who could benefit from immunotherapy, combination therapy might be an option.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Tong, W. Lu, Y. Zhang: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.