1723P - MicroRNA expression and DNA methylation profiles do not distinguish between primary and recurrent well-differentiated liposarcoma

Abstract

BackgroundApproximately one-third of the patients with well-differentiated liposarcoma (WDLPS) will develop a local recurrence after resection of the primary tumor. Not much is known about the molecular relationship between the primary tumor and the recurrent tumor, which is important to reveal potential drivers of recurrence. Here we investigated the biology of recurrent WDLPS by comparing paired primary and recurrent WDLPS using microRNA profiling and genome-wide DNA methylation analyses. MethodsPaired primary and recurrent WDLPS formalin-fixed and paraffin-embedded tumor samples were collected (N=27 pairs). MicroRNA expression profiles were determined using TaqMan® Low Density Array (TLDA) cards, capable of detecting 754 microRNAs. Genome-wide DNA methylation and differentially methylated regions were assessed by methylated DNA sequencing (MeD-seq). ResultsA supervised cluster analysis based on differentially expressed microRNAs between paired primary and recurrent WDLPS did not reveal a clear cluster pattern separating the primary from the recurrent tumors. The clustering was also not based on tumor localization, time to recurrence, age or the status of the resection margins. Changes in DNA methylation between primary and recurrent tumors were extremely variable, and no consistent DNA methylation changes were found. As a result, a supervised clustering analysis based on differentially methylated regions between primary and recurrent tumors did not show a distinct cluster pattern based on any of the features. Subgroup analysis for tumors localized in the extremity or the retroperitoneum also did not yield a clear distinction between primary and recurrent WDLPS samples. ConclusionsPrimary and recurrent WDLPS could not be distinguished based on microRNA expression and DNA methylation profiles and no common microRNA and DNA methylation alterations for recurrence could be identified. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.