Send to

Choose Destination
Int J Cancer. 2018 Dec 1;143(11):2828-2837. doi: 10.1002/ijc.31822. Epub 2018 Oct 4.

Fine mapping of 2q35 high-risk neuroblastoma locus reveals independent functional risk variants and suggests full-length BARD1 as tumor-suppressor.

Author information

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II", Naples, Italy.
CEINGE Biotecnologie Avanzate, Naples, Italy.
Division of Oncology and Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, PA.
Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
IRCCS SDN, Naples, Italy.
Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Hospital Sant Joan de Déu, Developmental Tumor Biology Laboratory and Department of Oncology, Esplugues de Llobregat, Barcelona, Spain.
Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA.
Department of Biostatistics, Epidemiology and Informatics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.


A previous genome-wide association study (GWAS) identified common variation at the BARD1 locus as being highly associated with susceptibility to high-risk neuroblastoma, but the mechanisms underlying this association have been not extensively investigated. Here, we performed a fine mapping analysis of BARD1 locus (2q35) using GWAS data from 556 high-risk neuroblastoma patients and 2,575 controls of European-American ancestry, and identified two independent genome-wide neuroblastoma-associated loci. Functional single-nucleotide polymorphism (SNP) prioritization identified two causative variants that independently contributed to neuroblastoma risk, and each replicated robustly in multiple independent cohorts comprising 445 high-risk cases and 3,170 controls (rs17489363: combined p = 1.07 × 10-31 , OR:1.79, 95% CI:1.62-1.98 and rs1048108: combined p = 7.27 × 10-14 , OR:0.65, 95% CI:0.58-0.73). Particularly, the T risk allele of rs17489363 in the canonical promoter region of full-length BARD1 altered binding site of the transcription factor HSF1 and correlated with low expression of full-length BARD1 mRNA and protein. Low-level expression of full-length BARD1 associated with advanced neuroblastoma. In human neuroblastoma cells, attenuating full-length BARD1 increased proliferation and invasion capacity. In conclusion, we have identified two potentially causative SNPs at the BARD1 locus associated with predisposition to high-risk neuroblastoma, and have shown that full-length BARD1 may act as tumor suppressor.


BARD1; GWAS; SNP; fine mapping.; neuroblastoma

[Available on 2019-12-01]
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center