Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition

Clin Genet. 2019 Oct;96(4):359-365. doi: 10.1111/cge.13600. Epub 2019 Jul 15.


Cancer predisposition syndromes (CPS) result from germline pathogenic variants, and they are increasingly recognized in the etiology of many pediatric cancers. Herein, we report the genetic/genomic analysis of 40 pediatric patients enrolled from 2016 to 2018. Our diagnostic workflow was successful in 50% of screened cases. Overall, the proportion of CPS in our case series is 10.9% (20/184) of enrolled patients. Interestingly, 12.5% of patients achieved a conclusive diagnosis through the analysis of chromosomal imbalance. Indeed, we observed germline microdeletions/duplications of regions encompassing cancer-related genes in 50% of patients undergoing array-CGH: EIF3H duplication in a patient with infantile desmoplastic astrocytoma and low-grade Glioma; SLFN11 deletion, SOX4 duplication, and PARK2 partial deletion in three neuroblastoma patients; a PTPRD partial deletion in a child diagnosed with glioblastoma multiforme. Finally, we identified two cases due to DICER1 germline mutations.

Keywords: cancer predisposition syndromes; genetic testing; genotype-phenotype relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Alleles
  • Child
  • Child, Preschool
  • DNA Copy Number Variations*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Genomics / methods
  • Germ-Line Mutation*
  • Humans
  • Infant
  • Male
  • Neoplasms / diagnosis
  • Neoplasms / genetics*