Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease

In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n=32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.

Automated summary

The study used Illumina Infinium Methylation array to investigate genome-wide methylation changes in soft tissue sarcomas during metastatic and recurrent disease, finding differential methylation in all matched samples and identifying novel genes involved in sarcoma progression. These findings suggest the presence of epigenetic differences across primary and metastatic/recurrent human tissue samples previously unreported.