(P 400) THE LANDSCAPE OF GENOMIC ALTERATIONS FROM 1494 SOFT TISSUE AND BONE SARCOMAS AT MD ANDERSON CANCER CENTER

Objective: Sarcomas comprise a relatively rare cancer type derived from connective tissues, though within this cancer type is a heterogeneous group of diseases with nearly 100 different histologic subtypes identified to date. We explored the landscape of genomic alterations and their potential clinical actionability in soft tissue and bone sarcomas with available clinical sequencing at MD Anderson Cancer Center.

Methods: This is a retrospective review of 1494 soft tissue and bone sarcoma cases seen at MD Anderson Cancer Center between 2007 and 2022 with available clinical sequencing data. Most patients had in-house clinical sequencing at MD Anderson. The MD Anderson Precision Oncology Decision Support (PODS) was used to assess for clinical actionability of genomic alterations.

Results: The cohort was mostly comprised of leiomyosarcoma (21.1%), gastrointestinal stromal tumor (15.9%), undifferentiated pleomorphic sarcoma (12.7%), chondrosarcoma (6.6%), and well-differentiated/dedifferentiated liposarcoma (6.5%). The most commonly mutated genes were TP53 (47.5%), RB1 (9.8%), and ATRX (7.4%). The most common copy number variants were seen in MDM2 (11.4%), CDK4 (10.4%), CDKN2A (4.4%), CDKN2B (3.6%), and RB1 (3.0%). The most commonly altered pathways or classes of genes were cell cycle regulators, transcription factors, epigenetic regulators, and DNA damage response. A potentially clinically actionable mutation was seen in 58.6% of sarcomas sequenced. Germline variants were seen in the following genes, potentially suggesting a genetic predisposition to sarcoma: KIT mutation in 6.6% of the cohort, MET in 5.5%, PIK3CA in 3.9%, and ATM in 3.0%. These germline variants were seen across the spectrum of sarcoma subtypes.

Conclusion: This study suggests that routine clinical next generation sequencing of sarcomas has the potential to open additional treatment options for patients with sarcoma. It also suggests the possibility of certain germline variants predisposing to sarcoma. These findings may inform additional preclinical and clinical studies of specific genomic alterations in specific sarcoma subtypes. Future work will be needed to assess the clinical impact of using these data and whether these genetic alterations are as predictive of outcomes in sarcomas as they are in other cancers.