Pan-cancer genome and transcriptome analyses of 1,699 pediatric leukemias and solid tumors

Dr. Stanley Pounds

Stan Pounds, PhD

Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalties and differences in key biological processes dysregulated in cancer cells from different lineages. Pan-cancer analyses have been performed for adult but not pediatric cancers. This study combined information across many pediatric cancers to offer more complete insights into this collection of rare diseases. The study analyzed molecular aberrations across multiple cancer types in 1,699 pediatric leukemias and solid tumors across six histotypes, with whole-exome, whole-genome, and transcriptome sequencing data processed under a uniform analytic framework. The genomic random interval statistical model was used to identify specific genes with the most significant overabundance of various aberrations in childhood cancers. We found 142 driver genes in pediatric cancers, of which only 45% match those found in adult pan-cancer studies. Copy number alterations and structural variants constituted 62% of the events. Eleven genome-wide mutational signatures were identified. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% had allele-specific expression. These findings reveal the genomic architecture for pediatric cancers and highlight the need to develop precision therapies specifically for pediatric cancer.

Full Citation

Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN, Gawad C, Zhou X, Li Y, Rusch MC, Easton J, Huether R, Gonzalez-Pena V, Wilkinson MR, Hermida LC, Davis S, Sioson E, Pounds S, Cao X, Ries RE, Wang Z, Chen X, Dong L, Diskin SJ, Smith MA, Auvil JMG, Meltzer PS, Lau CC, Perlman EJ, Maris JM, M S, Hunger SP, Gerhard DS, Zhang J.  Pan-cancer genome and transcriptome analyses of 1,699 pediatric leukemias and solid tumors. Nature, 555:371-376, 2018.