Comprehensive investigation of DNA damage repair genes in children with cancer identifies <i>SMARCAL1</i> as novel osteosarcoma predisposition gene.

ABSTRACT:

Background

Recent large-scale genomic sequencing studies reveal that 5-18% of children with cancer harbor pathogenic variants (PV) in known cancer predisposing genes (CPG). However, DNA damage repair (DDR) genes, which are frequently somatically altered in pediatric tumors, have not been systematically examined as a source of novel cancer predisposing signals.

Methods

To address this gap, we interrogated 189 genes across six DDR pathways for the presence of PV among 5,993 childhood cancer cases and 14,477 adult non-cancer controls. PV were defined as rare (allele frequency <0.05% in the gnomAD v2.1 non-cancer subset), nonsense, frameshift, affecting canonical splice sites, and missense with REVEL score >0.7. Using logistic and firth regression, we identified genes with stati

SUBMITTER: Oak N 

PROVIDER: S-EPMC12132114 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature