Classification of pediatric soft and bone sarcomas using DNA methylation-based profiling

Pediatric sarcomas present heterogeneous morphology, genetics and clinical behavior posing a challenge for an accurate diagnosis. DNA methylation is an epigenetic modification that coordinates chromatin structure and regulates gene expression, determining cell type and function. DNA methylation-based tumor profiling classifier for sarcomas (known as sarcoma classifier) from the German Cancer Research Center (Deutsches Krebsforschungszentrum) was applied to 122 pediatric sarcomas referred to a reference pediatric oncology hospital. The classifiers reported 88.5% of agreement between histopathological and molecular classification confirming the initial diagnosis of all osteosarcomas and Ewing sarcomas. The Ewing-like sarcomas were reclassified into sarcomas with BCOR or CIC alterations, later confirmed by orthogonal diagnostic techniques. Regarding the CNAs profile, osteosarcomas had several chromosomal gains and losses as well as chromothripsis, whereas Ewing sarcomas had few large events, such as amplifications of chromosomes 8 and 12. The molecular classification together with clinical and histopathological assessment could improve the diagnosis of pediatric sarcomas although there are limitations to deal with more rare classes. This study provides an increase in the number of sarcomas evaluated for DNA methylation profiling in the pediatric population.