This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.
- Integrated molecular characterization of the lethal pediatric cancer pancreatoblastoma.
- Paper ID
- Department of Pediatrics, Graduate School of Medicine, The University of Tokyo.
Cancer research, 2017
PMID: 29233928 (view at PubMed or Europe PMC)
- Pancreatoblastoma (PBL) is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multi-omics study of whole exome and RNA sequencing as well as genome-wide copy number and methylation analyses of 10 PBL cases. The PBL genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of CTNNB1 (90%) and copy-neutral loss of heterozygosity (CN-LOH) of APC (10%). In addition, imprinting dysregulation of IGF2 as a consequence of CN-LOH (80%), gain of paternal allele (10%), and gain of methylation (10%) were universally detected. At the transcriptome level, PBL exhibited an expression profile characteristic of early pancreas progenitor-like cells along with upregulation of the R-spondin/LGR5/RNF43 module. Our results offer a comprehensive description of the molecular basis for PBL and highlight rational therapeutic targets for its treatment.
- Paper Status