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

• Published in: PloS one Vol. 15; no. 1; p. e0228014
• Main Authors: Vos, Melissa, Boers, Ruben, Vriends, Anne L M, Boers, Joachim, van Kuijk, Patricia F, van Houdt, Winan J, van Leenders, Geert J L H, Wagrodzki, Michal, van IJcken, Wilfred F J, Gribnau, Joost, Grünhagen, Dirk J, Verhoef, Cornelis, Sleijfer, Stefan, Wiemer, Erik A C
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.01.2020; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Analysis; Biology and life sciences; Cluster Analysis; Clustering; Criminal investigation; Deoxyribonucleic acid; DNA; DNA fingerprinting; DNA methylation; DNA Methylation - genetics; DNA sequencing; Epigenetics; Female; Formaldehyde; Gene expression; Gene Expression Regulation, Neoplastic; Gene sequencing; Genetic Heterogeneity; Genomes; Genomics; Humans; Liposarcoma; Liposarcoma - genetics; Localization; Male; Medicine and Health Sciences; Methylation; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Neoplasm Recurrence, Local - genetics; Paraffin; Paraffins; Pathology; Physical Sciences; Principal Component Analysis; Recurrence (Disease); Research and Analysis Methods; Retroperitoneum; Ribonucleic acid; RNA; Subgroups; Surgery; Tumors; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0228014

Approximately one-third of the patients with well-differentiated liposarcoma (WDLPS) will develop a local recurrence. 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. In total, 27 paired primary and recurrent WDLPS formalin-fixed and paraffin-embedded tumor samples were collected. MicroRNA expression profiles were determined using TaqMan® Low Density Array (TLDA) cards. Genome-wide DNA methylation and differentially methylated regions (DMRs) were assessed by methylated DNA sequencing (MeD-seq). A 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 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 DMRs 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. In conclusion, microRNA expression profiles and DNA methylation profiles do not distinguish between primary and recurrent WDLPS and no putative common drivers could be identified.