TARGET Analysis Working Group
The TARGET Analysis Working Group (TAWG) uses comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of high-risk or hard-to-treat childhood cancers.
Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes dysregulated in cancer cells. Pan-cancer analyses have been performed for adult but not pediatric cancers, which commonly arise in developing mesoderm rather than adult epithelial tissues. The TARGET trans-cancer study of somatic alterations includes single nucleotide variants (SNVs), small insertion/deletions (indels), structural variations (SVs), copy number alterations (CNAs), gene fusions and internal tandem duplications (ITDs), in 1,699 pediatric leukemia and solid tumours across six histotypes. The TAWG reports 142 driver genes in pediatric cancers, of which only 45% matched those found in adult pan-cancer studies; CNAs and SVs constituted the majority (62%) of events. Eleven mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression of those protein-coding mutations for which the mutant allele transcription was detectable.
Whole-genome (WGS), whole-exome (WXS) and transcriptome (mRNA-seq) sequencing data were processed under a uniform analytical framework. These data provide a comprehensive genomic architecture for these childhood cancers and emphasize the need for the development of precision therapies for pediatric cancer.