Author:
Ma Xiaotu,Liu Yu,Liu Yanling,Alexandrov Ludmil B.,Edmonson Michael N.,Gawad Charles,Zhou Xin,Li Yongjin,Rusch Michael C.,Easton John,Huether Robert,Gonzalez-Pena Veronica,Wilkinson Mark R.,Hermida Leandro C.,Davis Sean,Sioson Edgar,Pounds Stanley,Cao Xueyuan,Ries Rhonda E.,Wang Zhaoming,Chen Xiang,Dong Li,Diskin Sharon J.,Smith Malcolm A.,Guidry Auvil Jaime M.,Meltzer Paul S.,Lau Ching C.,Perlman Elizabeth J.,Maris John M.,Meshinchi Soheil,Hunger Stephen P.,Gerhard Daniela S.,Zhang Jinghui
Abstract
Abstract
Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult1,2,3,4 but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues5. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.
Publisher
Springer Science and Business Media LLC