114P Real-world evidence of synovial sarcoma: Prognostic factors and therapeutic approaches from cancer registry data
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Conventional (CONV) and extraosseous/post-radiotherapy (EXRD) osteosarcoma are distinct clinical entities with different pathogeneses, but their specific molecular determinants remain undefined.In this study, we compared the genetic backgrounds of these subtypes to identify unique genomic alterations that may underlie distinct oncogenic mechanisms.Methods: We analyzed FFPE samples from the Universities of Pisa and Florence.Informed consent for genetic testing was obtained at diagnosis.DNA was extracted using the DNA FFPE Kit with EZ2 Connect (QiagenÔ).A custom gene panel was designed based on published WES data.Libraries were prepared with the DNA Prep with Enrichment Kit and run on NextSeq2000Ô (IlluminaÔ).Bioinformatic analysis used optimized pipelines and Pisces to reduce germline variant calls.Odds ratios and chi-squared tests with corrections were calculated as appropriate.Results: We analyzed FFPE samples from CONV (n¼48) and EXRD (n¼9).The top mutated genes in CONV were GNAQ (44%) and KMT2D (48%), with half of the GNAQ mutations being nonsense.In contrast, EXRD showed ATRX (78%), KMT2C (67%), and BRCA2 (67%) as the most mutated genes.The majority of the mutations were missense with the exception of ATRX, which also had frameshift and nonsense mutations.Comparing groups, only ATRX (OR¼0.053,p¼0.008) and DCC (OR¼0.050,p¼0.008) mutations were significantly enriched in EXRD (ATRX: 8.3% vs 66.7%; DCC: 14.6% vs 77.8%).Notably, 5/7 DCC mutations in EXRD affected the neogenin_C domain, critical for cell survival.Mutations in this domain may hinder DCC-mediated apoptosis under ligand-deprived conditions, potentially driving tumor survival in this subset of patients.
Source: ESMO Open
Authors: I. Surovtsova, J.T. Thiel, A. Daigeler, P. Morakis
Institutions: University of Tübingen, Krebsregister Baden-Württemberg
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,910
OpenAlex ID: W4408737146