To achieve more comprehensive genome-level analysis in our pediatric oncology patients, we utilized three CLIA-certified, CAP (College of American Pathologists), and New York State Department of Health approved assays. When possible, we utilized a cancer whole exome sequencing test (cWES) comprising WES of tumor and normal tissue (buccal swab or peripheral blood) and RNA sequencing (RNA-seq) of tumor tissue. This assay was optimized for fresh or frozen specimens. When sample adequacy was a concern, we also utilized a directed cancer gene panel assay which sequenced 467 cancer-associated genes and was optimized for use with formalin fixed paraffin embedded (FFPE) material (Columbia Comprehensive Cancer Panel, CCCP). If a constitutionally encoded disease was suspected (e.g. familial hemophagocytic lymphohistiocytosis), we performed constitutional WES from the patient and both parents (trio) when available.