Pediatric neoplasms have unique demands, including triaging of small biopsies for multiple testing modalities, and a pediatric cancer genome that is notably different from the adult cancer genome. Pediatric cancers are more likely to be driven by gene fusions and typically have a lower tumor mutational burden. Clinically relevant unique molecular targets exist within pediatric cancers, with important implications for diagnosis, prognosis, and treatment selection. Hence, assays and interpretation workflows must be designed thoughtfully to support molecular tumor profiling for children with cancer, including accommodation of small samples, detection of gene fusions, and consideration of potential germline associations.
Pediatric neoplasms have different genetics, and fusions are particularly common.
Small biopsies must be triaged to meet clinical demands.
The care of children with benign and malignant neoplasms is increasingly supported by molecular diagnostics.
Pediatric neoplasms are fundamentally different from adult neoplasms, with different diagnoses, tumor biology, tumor genomes, and treatment algorithms. Pediatric solid and brain tumors and hematologic malignancies are relatively rare compared to their adult counterparts. Although the volume of cases may be low, the clinical impact of a correct diagnosis on the life of a child deserves special consideration, even within our cost-constrained health care systems.
An informed and inclusive molecular diagnostic program will include workflows, assays, and interpretation processes which accommodate young patients with cancer. Considerations for pediatric tumors begin with preanalytical factors, including tissue acquisition and handling, continue through analytical testing and interpretation of a given assay, and persist to include downstream implications for the patient, including clinical interpretation of genetic alterations, adjuvant and neoadjuvant treatment selection, and consideration of germline cancer predisposition. In this review, we focus on the unique elements of performing molecular diagnostics tailored to a predominantly pediatric patient population with benign and malignant neoplasms.