Pan-cancer genome and transcriptome analyses of 1,699 pediatric leukemias and solid tumors
By Xiaotu Ma, Yu Liu, Yanling Liu, Ludmil B. Alexandrov, Michael N. Edmonson, Charles Gawad, Xin Zhou, Yongjin Li, M. Rusch, J. Easton and 23 more. Nature, 2018
750 citations recorded by the source corpus.
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 adult but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. 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.
Subfields: Cancer Research, Genetics, Neurology
View Paper: https://www.semanticscholar.org/paper/2fbef963de562322377c26856dfc3326067e5249
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Citations in the corpus
- The landscape of genomic alterations across childhood cancers (2018, neutral): “This study is biased towards central nervous system tumours, and is complemented by an additional study of a non-overlapping paediatric cohort with mainly leukaemias and extra-cranial solid tumours 9 .”
- Multi-omics Data Integration, Interpretation, and Its Application (2020, background): “21,22 Omics Discovery Index Omics Discovery Index (OmicsDI; https://www.omicsdi.org/) contains data sets from 11 repositories in a common data structure.”