BARD1 germline variants induce haploinsufficiency and DNA repair defects in neuroblastoma.

ABSTRACT:

Importance

High-risk neuroblastoma is a complex genetic disease that is lethal in 50% of patients despite intense multimodal therapy. Our genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) within the BARD1 gene showing the most significant enrichment in neuroblastoma patients, and also discovered pathogenic (P) or likely pathogenic (LP) rare germline loss-of-function variants in this gene. The functional implications of these findings remain poorly understood.

Objective

To define the functional relevance of BARD1 germline variation in children with neuroblastoma.

Design

We correlated BARD1 genotype with BARD1 expression in normal and tumor cells and the cellular burden of DNA damage in tumors. To validate

SUBMITTER: Randall MP 

PROVIDER: S-EPMC9915690 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature