Same but different the genetic causes of altered amino acid metabolism in pediatric and adult cancer

Abstract

Altered amino acid metabolism has become a hallmark of both pediatric and adult cancer. Glutamine, serine, glycine and arginine show additional uses beside protein synthesis to support cancer growth such as stimulating carbon metabolism through feeding the TCA cycle, regulating redox homeostasis, ROS defence and forming metabolites required for purine synthesis or methylation reactions. Here, we investigate how amino acid metabolism compares between pediatric and adult cancer, followed by the corresponding genetic causes in children and adults. Amino acid metabolism appears to be dysregulated by three key factors: increased transport, catabolism and de novo synthesis. Upregulated transporters are ASCT1, ASCT2, LAT1 and CAT1. Important metabolic enzymes with high activity in cancer are GLS1, PHGDH, PSAT1 ARG1 and ARG2. Although the metabolism is similarly altered in pediatric and adult cancer, the genetic causes show more differences. Adult cancer is often caused by somatic mutations in oncogenes and tumor suppressors, which alters signalling pathways like PI3K/AKT/mTOR or Wnt/β-catenin. Pediatric cancer is characterised by germline mutations, fusion genes and epigenetic dyrsregulation. By showing how comparable amino acid metabolism in cancer is between the age groups, we hope to stimulate broader investigation interchangeability of metabolic inhibitors.