Fine mapping of 2q35 high-risk neuroblastoma locus reveals independent functional risk variants and suggests full-length BARD1 as tumor-suppressor.
Fine mapping of 2q35 high-risk neuroblastoma locus reveals independent functional risk variants and suggests full-length BARD1 as tumor-suppressor.
复制标题
DOI：
10.1002/ijc.31822
复制
发表时间：
2018-12-01
影响因子：
6.4
通讯作者：
Capasso M
中科院分区：
文献类型：
--
作者：
Cimmino F;Avitabile M;Diskin SJ;Vaksman Z;Pignataro P;Formicola D;Cardinale A;Testori A;Koster J;de Torres C;Devoto M;Maris JM;Iolascon A;Capasso M
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 risk allele T of rs17489363 in the canonical promoter region of full-length BARD1 altered binding sites 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.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
3.5
作者：
Cimmino F;Formicola D;Capasso M
通讯作者：
Capasso M
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
4.5
作者：
McDaniel LD;Conkrite KL;Chang X;Capasso M;Vaksman Z;Oldridge DA;Zachariou A;Horn M;Diamond M;Hou C;Iolascon A;Hakonarson H;Rahman N;Devoto M;Diskin SJ
通讯作者：
Diskin SJ
影响因子：
3.4
作者：
Li Q;Martinez JD
通讯作者：
Martinez JD