DNA Methylation Profiles do not Distinguish between Primary and Recurrent Well-Differentiated Liposarcoma

Well-differentiated liposarcoma (WDLPS) recurs in approximately one-third of the patients. The molecular relationship between primary tumor and recurrent tumors is barely studied, but is important to reveal potential drivers of recurrence. Here we investigated the biology of recurrent WDLPS using 27 paired primary and recurrent WDLPS samples. Genome-wide DNA methylation and differentially methylated regions (DMRs) were assessed by methylated DNA sequencing (MeD-seq) (Boers R. et al. 2018, Genome-wide DNA methylation profiling using the methylation-dependent restriction enzyme LpnPI. Genome Res. 28: 88-99). In the supervised clustering analyses, no clear clustering separating the primary from the recurrent tumors, based on DMRs, was observed. The clustering was also not based on tumor localization, time to recurrence, age or status of the resection margins. Changes in DNA methylation between primary and recurrent tumors were extremely variable; no consistent DNA methylation changes were found. Subgroup analysis for tumors localized in the extremity or retroperitoneum also did not yield a clear distinction between primary and recurrent WDLPS. In conclusion, DNA methylation profiles do not distinguish between primary and recurrent WDLPS and no putative common drivers for recurrence could be identified.