Abstract 133P
Background
Evidence from retrospective and prospective studies highlights the significant impact of molecular profiling on clinical outcomes in sarcomas. It aids in diagnosis, informs prognosis and identifies actionable targets for directed systemic treatments. This study reports data from sarcomas submit-ted to our institution's in-house somatic comprehensive genome profiling (CGP) targeted gene panel platform.
Methods
Soft tissue sarcomas (STS), bone sarcomas (PBS), and gastrointestinal stromal tumors (GIST) submitted for CGP between January 2020 and September 2023 were analyzed. DNA and RNA were extracted from formalin-fixed paraffin-embedded (FFPE) samples, libraries were prepared according to Illumina Trusight Oncology 500 protocol and sequencing was run on the NextSeq 550 (Illumi-na). Data was retrospectively collected.
Results
A total of 39 patients had tumor samples sent for CGP. The cohort comprised 25 males and 14 females, with a median age of 54 years. STS were predominant (n=30), with undifferenti-ated pleomorphic sarcoma, uterine leiomyosarcoma, and leiomyosarcoma being the most frequent subtypes. Seven cases were PBS, and two were GIST. Median tumor mutational burden was 3.9 mut/Mb. Microsatellite instability was detected in a single case - chondro-sarcoma. Oncogenic alterations (Table) were identified in 31 (80%) of 39 tumor samples, with 17 findings considered actionable (28% of tests). The OncoKB grading level of evidence ranged from 1 to 4, of which 7 were grade 1.
Table: 133P
Most common oncogenic alterations found in sarcoma patients
| Alteration | N. |
| TP53 | 14 |
| RB1 | 6 |
| MDM2 | 4 |
| TMB-H | 3 |
| MUTYH | 3 |
| KDM6A | 3 |
| CDK4 | 3 |
| KIT | 3 |
| MYC | 2 |
| PAX3 | 2 |
| NF1 | 2 |
| MSH6 | 2 |
| PTEN | 2 |
| CCNE1 | 2 |
| TERT | 2 |
Conclusions
Despite the limitation of sample size, our study identified actionable alterations in 28% of tumor samples submitted to CGP. A high level of evidence of clinical activity according to OncoKB criteria was noted in 41% of actionable alterations. These findings underscore the importance of comprehensive genomic profiling in managing sarcomas.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Carmagnani Pestana: Financial Interests, Personal, Advisory Board: Bayer, Servier, Astellas; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Pfizer, Amgen, BMS, Merck, Knight therapeutics; Financial Interests, Institutional, Invited Speaker: Servier; Non-Financial Interests, Personal, Leadership Role: LACOG, SBOC. All other authors have declared no conflicts of interest.