CORRELATION OF CLINICAL FEATURES TO DNA METHYLATION-BASED PROGNOSTIC SUBTYPES IN CHORODOMA PATIENTS

Abstract

Abstract Chordomas are rare aggressive primary bone cancers affecting the skull-base and spine. We have previously identified robust DNA methylation-based prognostic groups, immune infiltrated and cellular subtypes. Here we further characterize these prognostic subtypes with an extensively annotated clinical database to identify factors that correlate with subtype, and investigate methylation patterns between existing clinical scoring systems groups. METHODS: 68 patients from a multi-institutional 20-year series were identified. These patients’ tumor samples had undergone whole genome DNA methylation profiling on the Illumina EPIC array. Baseline clinical features, including clinical features, treatment details, outcomes parameters and imaging were analyzed using chi-squared or kruskal-wallis test, and differential methylation patterns were examined between clinically distinct groups based on the Sekhar scoring system. RESULTS: Of all the variables tested, age of onset (p-value 0.012), location (skull base vs spine vs sacral: p-value 0.0365) and histological subtype (classical vs chondroid: p-value 0.0132) were the only significant predictors of subgroup placement; older age, spinal location, and classical histological typing were predictors of immune infiltrated chordoma subtype, which has a poorer clinical performance. As expected, death from chordoma was significantly different between subtypes (p-value 0.0056). Patients survival stratified based on Shakur grading, and clustered together on unsupervised hierarchical analysis on methylation. CONCLUSION: Overall, there are limited variables that correlate with methylation subtype, meaning that the epigenetic chordoma subtypes cannot be reliably identified using clinical or imaging features in the absence of molecular data. However clinical grading systems remain a valuable tool for prognostication, and display distinct methylation patterns.