(P 13) GENOMIC PROFILING OF ADULT SOFT TISSUE SARCOMAS FROM A SINGLE CENTER EXPERIENCE

Objective: One barrier to improving outcomes in patients with soft tissue sarcomas (STS) is the genomic and biologic complexity of these tumors. High-throughput molecular analysis (NGS) can enhance our understanding of sarcoma tumorigenesis. The genetic alterations identified by NGS can be used to define the molecular profile and identify potential predictive or prognostic biomarkers. This is because STS harbor genetic alterations that, in some cases, may be clinically actionable. The study of these alterations in routine clinical practice could contribute to improving the diagnosis, treatment, and prognosis of patients with these tumors. In this work, 69 STS tumor samples were sequenced to identify genomic alterations that may be actionable, predictors of tumor relapse, or specific to tumor subtype.

Methods: Tumor tissue sections were selected by an expert pathologist. Genomic DNA was isolated and purified from FFPE tumor tissues, using GeneReadTM DNA FFPE Kit. Library construction and target enrichment was performed using components from QIAseq Targeted DNA Panels, libraries were sequenced on NextSeq500 High output platform (Illumina) with 800M paired-end reads and 2500x mean coverage (based on 2 x 151bp paired-end read) following manufacturer’s user manual. Clinical and pathological data were collected for descriptive purposes and for correlation with molecular data results.

Results: A total of 69 patients diagnosed with STS were included in the study. The median age at diagnosis was 59 years (range 24–91 years). 40 (58%) of the cases were male and 29 (42%) were female. The most common histological subtypes were synovial sarcoma (16%, n=11), dedifferentiated liposarcoma (15%, n=10), undifferentiated pleomorphic sarcoma (13%, n=9) and liposarcoma (12%, n=8). The analysis of the results revealed that, without differentiating by histological subtype, the most frequently altered genes were NF1, TP53, APC, PTEN and KMT2D. Furthermore, the most affected signaling pathways were the DNA damage and repair pathway, the MAPK/PI3K-Akt pathway, the MAPK/mTOR/PI3K-Akt pathway, and the chromatin modulation pathway. Regarding actionability, more than half of the variants identified in STS samples were described as FDA-level 1 (FDA-recognized biomarkers predictive of response to an FDA-approved drug). These results were consistent with those of other studies that had been reviewed.

Conclusion: Our study describes the mutation profile of 33 patients with soft tissue sarcoma (STS) from a single center. The knowledge of the genomic alterations present in STS may facilitate more effective clinical management of these patients, in terms of diagnosis, prognosis, or therapeutic decisions.