Accurate Prediction of Central Conventional Chondrosarcoma Risk and Outcome Using Methylation Profiling: CHROME

Area of Science:

• Oncology
• Molecular Pathology
• Genomics

Background:

• Chondrosarcomas are malignant bone tumors with variable behavior, making prognostication difficult.
• Current histological grading has high interobserver variability, impacting clinical management.
• DNA methylation profiling is emerging as a valuable tool in surgical pathology.

Purpose of the Study:

• To investigate the prognostic value of DNA methylation profiling in central conventional chondrosarcoma.
• To develop a novel risk score for predicting patient outcomes.

Main Methods:

• Generated DNA methylation data from 69 central conventional chondrosarcomas using Illumina's Human MethylationEPIC Array.
• Applied LASSO Cox regression to identify eight informative methylation sites.
• Constructed a risk score, CHROME (Chondrosarcoma Risk Outcome from Methylation), based on identified methylation sites.

Main Results:

• CHROME successfully stratified patients into High or Low risk groups for disease recurrence, metastasis, and mortality.
• Validation in an independent cohort (n=68) showed strong discriminatory performance with complete outcome separation.
• CHROME correctly reclassified cases, including a low-grade tumor with an event into the High risk group and high-grade tumors without events into the Low risk group.

Conclusions:

• CHROME provides accurate risk stratification for central conventional chondrosarcoma.
• This DNA methylation-based tool may significantly improve prognostication and clinical management.
• CHROME offers a more reliable alternative to traditional histological grading.