Next-Generation Sequencing Approaches to Characterize Genomic Predisposition of Solid Tumors in Children, Adolescents, and Young Adults (C-AYA)

摘要: Compared to adult carcinomas, there is a paucity of targeted treatments for solid tumors in children, adolescents, and young adults (C-AYA). The impact of germline genomic signatures has implications for heritability, but its impact on targeted treatment selection has not been fully appreciated. To address this gap, we performed variant-prioritization analysis, based on the American College of Medical Genetics and Genomics (ACMG) classification guidelines, on germline exome sequencing data of 1,507 C-AYA patients with solid tumors. We identified 12% of these patients carrying germline pathogenic and/or likely pathogenic (P/LP) mutations in 54 of 204 known cancer-predisposing genes (KCPG), including RB1, NF1, and TP53, while adding 1 to 19 unexpected KCPG for each of adrenocortical carcinoma, astrocytoma, CNS tumors, Ewing sarcoma, neuroblastoma, osteosarcoma, retinoblastoma, soft tissue …