Cancer-Predisposition Genetic Analysis in Children with Brain Tumors Treated at a Single Institution in Japan

Oncology. 2022;100(3):163-172. doi: 10.1159/000521621. Epub 2021 Dec 27.


Brain tumors affect one-third of all children with cancer. Approximately 10% of children with cancer carry variants in cancer-predisposition genes. However, germline analyses in large cohorts of Asian children have not been reported. Thirty-eight Japanese patients with pediatric brain tumors were included in this study (19 boys, 19 girls). DNA was extracted from the patients' peripheral blood, and cancer-associated genes were analyzed using targeted resequencing. Rare variants with allele frequencies <0.1% in the general population and variants suspected to be pathogenic were extracted and analyzed. Pathogenic variants were found in 7 patients (18%): 2 nonsense variants of CHEK2 and FANCI; 2 frameshift deletions in SMARCB1 and PTCH1; and 3 missense variants of TSC1, WRN, and MLH1. The median age at diagnosis was 9.1 years, and three of the 7 patients had a family history of cancer. One patient diagnosed with basal cell nevus syndrome, also called Gorlin syndrome, developed a second neoplasm, and another with an SMARCB1 variant and an atypical teratoid/rhabdoid tumor developed a thyroid adenomatous nodule. This is the first cancer-related germline analysis with detailed clinical information reported in Japanese children with brain tumors. The prevalence was almost equivalent to that in white children.

Keywords: Asians; Germline analysis; Hereditary cancer; Pediatric brain tumors.

MeSH terms

  • Adolescent
  • Brain Neoplasms / genetics*
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Male
  • MutL Protein Homolog 1 / genetics
  • Mutation*
  • Patched-1 Receptor / genetics
  • SMARCB1 Protein / genetics
  • Tuberous Sclerosis Complex 1 Protein / genetics
  • Werner Syndrome Helicase / genetics


  • MLH1 protein, human
  • PTCH1 protein, human
  • Patched-1 Receptor
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • TSC1 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • MutL Protein Homolog 1
  • WRN protein, human
  • Werner Syndrome Helicase