DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Metastasis at diagnosis in osteosarcoma. The EFO term metastasis measurement, date of diagnosis, osteosarcoma was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: metastasis measurement, date of diagnosis, osteosarcoma

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

L Mirabello, R Koster, BS Moriarity, LG Spector, PS Meltzer, J Gary, MJ Machiela, N Pankratz, OA Panagiotou, D Largaespada, Z Wang, JM Gastier-Foster, R Gorlick, C Khanna, SR de Toledo, AS Petrilli, A Patiño-Garcia, L Sierrasesúmaga, F Lecanda, IL Andrulis, JS Wunder, N Gokgoz, M Serra, C Hattinger, P Picci, K Scotlandi, AM Flanagan, R Tirabosco, MF Amary, D Halai, ML Ballinger, DM Thomas, S Davis, DA Barkauskas, N Marina, L Helman, GM Otto, KL Becklin, NK Wolf, MT Weg, M Tucker, S Wacholder, JF Fraumeni, NE Caporaso, JF Boland, BD Hicks, A Vogt, L Burdett, M Yeager, RN Hoover, SJ Chanock, SA Savage

TITLE:

A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma.

JOURNAL:

Cancer discovery Sep 2015, Vol 5, pp. 920-31

ABSTRACT:

Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.2 × 10(-9); OR, 2.43; 95% confidence interval, 1.83-3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that NFIB is an osteosarcoma metastasis susceptibility gene. PUBMED: 26084801
Find other GeneSets from this publication