The Impact of Microenvironment on the Synovial Sarcoma Transcriptome

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Synovial sarcoma (SS) is a rare soft tissue sarcoma characterized by a specific chromosomal translocation, t(X;18), leading to the SS18-SSX fusion oncogene.
• Limited availability of well-characterized SS cell lines and a lack of direct comparison with their originating tumors hinder comprehensive research.

Purpose of the Study:

• To compare the transcriptomic profiles of matched synovial sarcoma tumor and cell line pairs.
• To investigate the influence of the tumor microenvironment on gene expression in SS.

Main Methods:

• RNA sequencing (RNAseq) was performed on three matched tumor and cell line pairs from a genetically engineered mouse model of SS.
• RNAseq was also conducted on two matched human SS tumor and cell line pairs.
• Transcriptomic data were analyzed to identify differentially expressed genes and assess similarities between tumors and their derived cell lines.

Main Results:

• Significant transcriptomic deviations were observed between mouse SS tumors and their derivative cell lines, with similar findings in human pairs.
• Differentially expressed genes primarily implicated inflammatory infiltrates and metabolic pathways, suggesting environmental influence.
• Transcriptomic profiles showed greater similarity among different SS tumors than between any tumor and its corresponding cell line; direct xenografts more closely resembled primary tumors than cell lines.

Conclusions:

• Synovial sarcoma cell lines do not accurately recapitulate the transcriptome of their originating tumors.
• The tumor microenvironment, particularly immune interactions and metabolism, profoundly impacts SS tumor transcriptomes.
• Findings underscore the importance of considering environmental factors when studying SS and developing therapeutic strategies.