Comprehensive Genomic Characterization of Congenital and Infantile Cancers Reveals High Yield of Medically Meaningful Findings

PURPOSE We describe findings from genomic profiling of tumors among infantile pediatric patients studied within a translational research protocol established at our pediatric tertiary care center. Comprehensive genomic profiling was initiated to aid in diagnosis, prognostication, treatment, and detection of germline disease predisposition in this patient cohort. METHODS Enhanced exome sequencing of disease and comparator tissue was coupled with RNA sequencing of the disease-involved specimen to assess for single nucleotide variation, insertion/deletions, copy number alteration, structural variation, fusions, and methylation profiling–based tumor classification scores. RESULTS Among 317 patients who consented to the protocol, 39 (12%) had infantile cancers diagnosed at ≤1 year of age. Germline genetic alteration was frequent with 11 of 39 patients (28%) harboring a pathogenic change. Clinically relevant findings affecting diagnosis, prognosis, therapy, or surveillance were identified in 37 of 39 (95%) patients. CONCLUSION Our data support that a pediatric cohort gains significant benefit from a comprehensive profiling approach, with a high yield of clinically significant findings. Nearly half of the infants in this cancer cohort harbored tumors potentially susceptible to therapeutic targets on the basis of genomic profile, and among these, another half sought benefit from therapeutic implementation.