Abstract
Osteosarcoma is the most common primary tumor of bone. Osteosarcomas are rare in humans, but occur more commonly in dogs. A comparative approach to studying osteosarcoma has highlighted many clinical and biologic aspects of the disease that are similar between dogs and humans; however, important species-specific differences are becoming increasingly recognized. In this review, we describe risk factors for the development of osteosarcoma in dogs and humans, including height and body size, genetics, and conditions that increase turnover of bone-forming cells, underscoring the concept that stochastic mutational events associated with cellular replication are likely to be the major molecular drivers of this disease. We also discuss adaptive, cancer-protective traits that have evolved in large, long-lived mammals, and how increasing size and longevity in the absence of natural selection can account for the elevated bone cancer risk in modern domestic dogs.
Highlights
Osteosarcoma is the most common primary tumor of bone in both dogs and humans.Osteosarcomas are rare in humans, with fewer than 1,000 new cases diagnosed annually [1]
A second, smaller peak occurs in the occurring as a second or later malignancy (24.3%) [1,13], or concomitantly with Paget’s disease (9.5%), elderly [1,13], with many osteosarcoma cases in individuals over 60 years of age occurring as a second which is characterized by abnormal bone turnover in the aging (>55 year old) skeleton [14]
Additional germline variants commonly seen in human osteosarcoma cases (RB, TP53, and NFIB) were uncommon in this canine cohort, occurring in only one case each [121]
Summary
Osteosarcoma is the most common primary tumor of bone in both dogs and humans. Osteosarcomas are rare in humans, with fewer than 1,000 new cases diagnosed annually [1]. Peak incidence of osteosarcoma in humans occurs in adolescents and young adults comprises approximately 6 to 8% of cases in dogs under 3 years of age (juveniles and young adults). A second, smaller peak occurs in the occurring as a second or later malignancy (24.3%) [1,13], or concomitantly with Paget’s disease (9.5%), elderly [1,13], with many osteosarcoma cases in individuals over 60 years of age occurring as a second which is characterized by abnormal bone turnover in the aging (>55 year old) skeleton [14]. This represents an approximately 30-fold increase compared to the general uncommon complication of Paget’s disease, occurring in an estimated 1 in 650 patients This population >40 years old [15]. Represents an approximately 30-fold increase compared to the general population >40 years old [15]
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