Tackling the mysteries of osteosarcoma in children by uncovering gene variants associated with risk



Osteosarcoma is the most common malignant bone tumor in children and adolescents External link. However, researchers know very little about its common genetic risk factors, partly due to the tumor’s rarity in the general population: there are approximately 800 new cases in the United States each year External link.


IRP investigators lead by Sharon Savage, M.D., completed the first genome-wide association study of genetic risk variants for osteosarcoma. The researchers discovered that osteosarcoma patients with specific variants in different genetic loci—within the glutamate receptor metabotropic 4 (GRM4) gene and on chromosome 2p25.2—were at significantly increased risk of osteosarcoma.


If validated in other populations, the identified genetic markers could serve as a tool that helps researchers find new mechanisms of osteosarcoma development and possibly help clinicians diagnose individuals at risk of osteosarcoma. In addition, IRP researchers are leading analyses to uncover genetic factors associated with osteosarcoma clinical outcomes, such as metastasis or response to therapy.


Savage SA, Mirabello L, Wang Z, Gastier-Foster JM, Gorlick R, Khanna C, Flanagan AM, Tirabosco R, Andrulis IL, Wunder JS, Gokgoz N, Patiño-Garcia A, Sierrasesúmaga L, Lecanda F, Kurucu N, Ilhan IE, Sari N, Serra M, Hattinger C, Picci P, Spector LG, Barkauskas DA, Marina N, de Toledo SR, Petrilli AS, Amary MF, Halai D, Thomas DM, Douglass C, Meltzer PS, Jacobs K, Chung CC, Berndt SI, Purdue MP, Caporaso NE, Tucker M, Rothman N, Landi MT, Silverman DT, Kraft P, Hunter DJ, Malats N, Kogevinas M, Wacholder S, Troisi R, Helman L, Fraumeni JF Jr, Yeager M, Hoover RN, Chanock SJ. (2013). Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nat Genet. 45(7), 799-803.

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This page was last updated on Tuesday, June 20, 2023