Osteosarcoma is an often fatal form of bone cancer occurring in humans, especially in children and adolescents. Osteosarcoma spontaneously occurs in dogs, and every year almost 10 times as many dogs compared to humans are diagnosed with osteosarcoma. In contrast to human osteosarcoma, canine osteosarcoma typically affects middle-aged dogs from large breeds such as golden retrievers, Rottweilers and greyhounds.  Dogs weighing more than 25 kg account for 90% of all cases of osteosarcoma. Our group and collaborators have identified TP53 and histone methyltransferase SETD2 as frequently mutated genes in canine osteosarcoma. TP53 is a well known tumour suppressor gene, and while SETD2 has known roles in multiple cancers, it has not previously been implicated in osteosarcoma. In an earlier study we also identified several germline variants located in genes that were associated with a predisposition to osteosarcoma. We continue to look for both inherited and tumor specific mutations in multiple breeds.

Scientific publications:

Letko A, Minor KM, Norton EM, Marinescu VD, Drögemüller M, Ivansson E, Megquier K, Noh HJ, Starkey M, Friedenberg SG, Lindblad-Toh K, Mickelson JR, Drögemüller C. 2021. Genome-Wide Analyses for Osteosarcoma in Leonberger Dogs Reveal the CDKN2A/B Gene Locus as a Major Risk Locus. Genes. 2021 Dec 9;12(12):1964. doi: 10.3390/genes12121964.

Sakthikumar, S., Elvers, I., Kim, J., Arendt, M.L., Thomas, R., Turner-Maier, J., Swofford, R., Johnson, J., Schumacher, S.E., Alföldi, J., Axelsson, E., Couto, C.G., Kisseberth, W.C., Pettersson, M.E., Getz, G., Meadows, J.R.S., Modiano, J.F., Breen, M., Kierczak, M., Forsberg-Nilsson, K., Marinescu, V.D., Lindblad-Toh, K., 2018. SETD2 Is Recurrently Mutated in Whole-Exome Sequenced Canine Osteosarcoma. Cancer Research 78, 3421–3431. doi:10.1158/0008-5472.CAN-17-3558

Karlsson, E.K., Sigurdsson, S., Ivansson, E., Thomas, R., Elvers, I., Wright, J., Howald, C., Tonomura, N., Perloski, M., Swofford, R., Biagi, T., Fryc, S., Anderson, N., Courtay-Cahen, C., Youell, L., Ricketts, S.L., Mandlebaum, S., Rivera, P., Euler, von, H., Kisseberth, W.C., London, C.A., Lander, E.S., Couto, G., Comstock, K., Starkey, M.P., Modiano, J.F., Breen, M., Lindblad-Toh, K., 2013. Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B. Genome Biology 14, R132–16. doi:10.1186/gb-2013-14-12-r132