TY - GEN AB - 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. AD - University of Chicago AD - University of Chicago AU - Yang, Yang AU - Yang, Lixing DA - 2023-10-17 ID - 9131 JF - Cell Report KW - CP: Cancer KW - chromothripsis KW - gene fusion KW - genome instability KW - genomic rearrangement L1 - https://knowledge.uchicago.edu/record/9131/files/Somatic-structural-variation-signatures-in-pediatric-brain-tumors.pdf L1 - https://knowledge.uchicago.edu/record/9131/files/1-s2.0-S2211124723012883-fx1_lrg.jpg L1 - https://knowledge.uchicago.edu/record/9131/files/Supplemental-information.zip L2 - https://knowledge.uchicago.edu/record/9131/files/Somatic-structural-variation-signatures-in-pediatric-brain-tumors.pdf L2 - https://knowledge.uchicago.edu/record/9131/files/1-s2.0-S2211124723012883-fx1_lrg.jpg L2 - https://knowledge.uchicago.edu/record/9131/files/Supplemental-information.zip L4 - https://knowledge.uchicago.edu/record/9131/files/Somatic-structural-variation-signatures-in-pediatric-brain-tumors.pdf L4 - https://knowledge.uchicago.edu/record/9131/files/1-s2.0-S2211124723012883-fx1_lrg.jpg L4 - https://knowledge.uchicago.edu/record/9131/files/Supplemental-information.zip LA - eng LK - https://knowledge.uchicago.edu/record/9131/files/Somatic-structural-variation-signatures-in-pediatric-brain-tumors.pdf LK - https://knowledge.uchicago.edu/record/9131/files/1-s2.0-S2211124723012883-fx1_lrg.jpg LK - https://knowledge.uchicago.edu/record/9131/files/Supplemental-information.zip N2 - 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. PY - 2023-10-17 T1 - Somatic structural variation signatures in pediatric brain tumors TI - Somatic structural variation signatures in pediatric brain tumors UR - https://knowledge.uchicago.edu/record/9131/files/Somatic-structural-variation-signatures-in-pediatric-brain-tumors.pdf UR - https://knowledge.uchicago.edu/record/9131/files/1-s2.0-S2211124723012883-fx1_lrg.jpg UR - https://knowledge.uchicago.edu/record/9131/files/Supplemental-information.zip Y1 - 2023-10-17 ER -