This is a genome-wide association study (GWAS) of osteosarcoma, the most common primary bone malignancy. Osteosarcoma has a bi-modal age distribution, the first peek in adolescence and young adulthood, the second after age 65. It occurs at increased frequency in several inherited cancer predisposition syndromes but the genetic contribution to sporadic osteosarcoma is largely unexplored. The objective of this study is to identify genetic risk factors for osteosarcoma through GWAS.
The investigators developed collaborations with multiple institutions in order to attain the necessary sample size required to discover novel loci in the genome associated with osteosarcoma using the GWAS approach. Genomic DNA (either blood or buccal in source) derived from osteosarcoma cases was obtained from each participating institution or research group. Findings are detailed in the publication below.
We subsequently conducted a multi-stage GWAS of metastasis at diagnosis of osteosarcoma in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis and showed that the risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. These findings are described in detail in the publication below.
Collaborating institutions included: The Children’s Oncology Group (COG); the Harvard School of Dental Medicine, USA; Universidad de Navarra, Pamplona, Spain; Institut Curie, France; Rizzoli Instituti, Bologna, Italy; Royal Orthopaedic Hospital, London, UK; University of Toronto, Litwin Centre for Cancer Genetics, Canada; Instituto de Oncologia Pediátrica GRAACC/UNIFESP, Brazil; Ankara Oncology and Education Research Hospital, Ankara, Turkey; the Peter MacCallum Cancer Centre, and the Kinghorn Cancer Centre, Garvan Institute of Medical Research, Australia; and the Children’s Oncology Group study at the University of Minnesota.