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

Autoři: Melissa Vos aff001;  Ruben Boers aff003;  Anne L. M. Vriends aff001;  Joachim Boers aff003;  Patricia F. van Kuijk aff001;  Winan J. van Houdt aff004;  Geert J. L. H. van Leenders aff005;  Michal Wagrodzki aff006;  Wilfred F. J. van IJcken aff007;  Joost Gribnau aff003;  Dirk J. Grünhagen aff002;  Cornelis Verhoef aff002;  Stefan Sleijfer aff001;  Erik A. C. Wiemer aff001
Působiště autorů: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands aff001;  Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands aff002;  Department of Developmental Biology, Erasmus University Medical Center, Rotterdam, the Netherlands aff003;  Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands aff004;  Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands aff005;  Department of Pathology, Maria Skłodowska-Curie Institute-Oncology Center, Warsaw, Poland aff006;  Center for Biomics, Erasmus University Medical Center, Rotterdam, the Netherlands aff007
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/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.

Klíčová slova:

DNA methylation – Gene pool – Hierarchical clustering – Methylation – MicroRNAs – Surgical resection – Tumor resection – Liposarcoma


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