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Radiotherapy Response Prediction in Myxofibrosarcomas and Undifferentiated Soft Tissue Sarcomas Using DNA Methylation

Tony G Kleijn1,2, Baptiste Ameline3, Wierd Kooistra1

  • 1Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

International Journal of Surgical Pathology
|January 29, 2026
PubMed
Summary

Myxofibrosarcoma and undifferentiated soft tissue sarcoma may be the same disease. DNA methylation profiling did not predict radiotherapy response, but chromosome 11q24.1 loss shows potential as a biomarker.

Keywords:
DNA methylationcopy number variationmyxofibrosarcomaprofilingradiotherapy responseundifferentiated soft tissue sarcoma

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Methylated DNA Immunoprecipitation
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Area of Science:

  • Oncology
  • Genomics
  • Cancer Biomarkers

Background:

  • Myxofibrosarcoma (MFS) and undifferentiated soft tissue sarcoma (USTS) are common, overlapping sarcoma subtypes.
  • Neoadjuvant radiotherapy followed by surgery is standard treatment, but response is unpredictable.
  • Predictive biomarkers for radiotherapy response are needed.

Purpose of the Study:

  • To investigate DNA methylation and copy number variation (CNV) profiles from pre-radiotherapy biopsies.
  • To identify predictive biomarkers for radiotherapy response in MFS and USTS.

Main Methods:

  • Analyzed DNA methylation and CNV data from 49 pre-radiotherapy sarcoma biopsies.
  • Correlated genomic data with radiotherapy response assessed by EORTC-STBSG criteria.
  • Utilized Illumina MethylationEPIC BeadChips for genome-wide profiling.

Main Results:

  • MFS, USTS, and pleomorphic liposarcomas formed a single, heterogeneous methylation cluster.
  • CNV profiles did not distinguish MFS from USTS.
  • No significant differences in methylation patterns between responders and non-responders.
  • Chromosome 11q24.1 loss was significantly more frequent in responders (100%) than non-responders (33%).

Conclusions:

  • MFS and USTS may represent a disease spectrum.
  • DNA methylation profiling is not a reliable predictor of radiotherapy response.
  • Chromosome 11q24.1 loss is a potential predictive biomarker requiring further validation.