Clinical utility of sarcoma methylation classifiers in soft tissue sarcoma diagnosis

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Soft tissue sarcomas are rare, heterogeneous tumors requiring accurate diagnosis.
• Histopathology and molecular testing are used, but diagnosis remains challenging.
• DNA methylation profiling offers an objective classification method with limited clinical implementation data in sarcomas.

Purpose of the Study:

• To evaluate the clinical utility of DNA methylation profiling for soft tissue sarcoma classification.
• To compare two versions (V12.3 and V13.1) of a sarcoma methylation classifier.
• To assess the diagnostic agreement between methylation profiling and histopathology.

Main Methods:

• Single-center study involving 40 tumor samples from 34 patients.
• Routine histopathology and array-based DNA methylation profiling were performed.
• Samples were classified using sarcoma methylation classifier versions V12.3 and V13.1.

Main Results:

• Version V12.3 achieved high classification scores (≥0.9) in 40% of samples, with 87.5% agreement with histopathology.
• Version V13.1 achieved high scores in 72.5% of samples, with 96.6% agreement with histopathology.
• V13.1 demonstrated a substantial improvement in classification confidence and agreement.

Conclusions:

• DNA methylation profiling is a valuable adjunct for confirming or refining soft tissue sarcoma diagnoses.
• The V13.1 classifier significantly enhanced diagnostic confidence and agreement over V12.3.
• Further optimization is needed for routine clinical implementation due to a subset of specimens lacking high-confidence classification.