Fig. 1. Model for integrative genomic analysis of pediatric cancers in clinical practice.

Comprehensive cytogenomic and molecular assays are performed at diagnosis to determine genomic or epigenetic alterations in the tumor. Pathogenic germline variants, as well as DNA variants that reflect ancestry and influence drug metabolism (pharmacogenomics), are determined by analysis of normal tissues, typically blood or fibroblasts. Results from these assays are integrated to refine diagnosis and select therapy. Focused gene-specific assays are performed for a subset of patients to determine whether pathogenic germline variants are de novo or inherited from a parent. Carriers should be counseled regarding recurrence risk and enrolled in a surveillance program (imaging, blood work) for early detection of cancer. In the relapse setting, focused assays may be used to determine whether the same genetic events that were detected at diagnosis are present. In addition, comprehensive cytogenomic and molecular assays should be used to identify novel genetic alterations that would dictate the need for alternative therapy.