Brain cancer is the leading cause of cancer-related death in children.
Somatic structural variations (SVs), large-scale alterations in DNA, remain
poorly understood in pediatric brain tumors. Here, we detect a total of
13,199 high-confidence somatic SVs in 744 whole-genome sequences of
pediatric brain tumors from the Pediatric Brain Tumor Atlas. The somatic SV
occurrences have tremendous diversity among the cohort and across different
tumor types. We decompose mutational signatures of clustered complex SVs,
non-clustered complex SVs, and simple SVs separately to infer their
mutational mechanisms. Our finding of many tumor types carrying unique sets
of SV signatures suggests that distinct molecular mechanisms shape genome
instability in different tumor types. The patterns of somatic SV signatures
in pediatric brain tumors are substantially different from those in adult
cancers. The convergence of multiple SV signatures on several major cancer
driver genes implies vital roles of somatic SVs in disease progression.