Negri GL, Grande BM, Delaidelli A, et al. - Researchers conducted an integrated whole-genome and exome sequencing analysis of paired primary and metastatic pediatric osteosarcoma specimens to recognize recurrent genomic alterations. Sequencing of 13 osteosarcoma patients comprising 13 primary, 10 metastatic, and three locally recurring tumors exhibited a highly heterogeneous mutational landscape, including cases of hypermutation and microsatellite instability positivity, although with virtually no recurrent alterations except for mutations including the tumor suppressor genes RB1 and TP53. At the germline level, alterations in multiple cancer-related genes in the majority of the cohort were discovered, including those potentially disrupting DNA damage response pathways. Metastases clutched only a minimal number of short variants from their similar primary tumors, while greater conservation was exhibited by copy number alterations. One recurrently amplified gene, KDR, was highly expressed in advanced cases and correlated with poor prognosis.