Comparative Aspects of Osteosarcoma Pathogenesis in Humans and Dogs

Fan, Timothy M.; Khanna, Chand

doi:10.3390/vetsci2030210

Cited by 42 publications

(42 citation statements)

References 132 publications

(162 reference statements)

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“…OS primarily affects adult dogs after growth plate closure, a distinct difference noted between the canine and human disease and further validated here (dog median age: 8.8 years, interquartile range 7‐10.4 years). Nevertheless, risk of OS is still speculated to be associated in part with skeletal development and growth in dogs, as it is in humans.…”

Section: Discussionsupporting

confidence: 71%

“…In contrast, spontaneous OS is much more common in dogs, with an estimated annual incidence of at least 139 cases per million dogs, and the similarities between canine OS and human OS, including natural occurrence, clinical presentation, prognostic factors, genetic aberrations, dysregulation of key molecular pathways, biological behaviors, and metastatic progression, suggest that conserved pathways are required to develop the OS phenotype . However, OS primarily occurs in mid‐aged to older dogs after growth plates have closed, a distinct difference between the human and canine disease.…”

Section: Introductionmentioning

confidence: 99%

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A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma

et al. 2019

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Background Canine osteosarcoma (OS) is a relevant spontaneous model for human OS. Identifying similarities in clinical characteristics associated with metastasis at diagnosis in both species may substantiate research aimed at using canine OS as a model for identifying mechanisms driving distant spread in the human disease. Methods This retrospective study included dog OS cases from three academic veterinary hospitals and human OS cases from the Surveillance, Epidemiology, and End Results program. Associations between clinical factors and metastasis at diagnosis were estimated using logistic regression models. Results In humans, those with trunk tumors had higher odds of metastasis at diagnosis compared to those with lower limb tumors (OR = 2.38, 95% CI: 1.51, 3.69). A similar observation was seen in dogs with trunk tumors compared to dogs with forelimb tumors (OR = 3.28, 95% CI 1.36, 7.50). Other associations were observed in humans but not in dogs. Humans aged 20‐29 years had lower odds of metastasis at diagnosis compared to those aged 10‐14 years (OR = 0.67, 95% CI: 0.47, 0.96); every 1‐cm increase in tumor size was associated with a 6% increase in the odds of metastasis at diagnosis (95% CI: 1.04, 1.08); compared to those with a white, non‐Hispanic race, higher odds were observed among those with a black, non‐Hispanic race (OR: 1.51, 95% CI: 1.04, 2.16), and those with a Hispanic origin (OR 1.35, 95% CI: 1.00, 1.81). Conclusion A common mechanism may be driving trunk tumors to progress to detectable metastasis prior to diagnosis in both species.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma

et al. 2019

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“…Ideally, OS research would use a more integrated approach, testing novel regimens across collections of diverse models, with laboratory experiments that educate human clinical trials 91 and canine clinical trials, 40,44 and vice versa. Each study, each experiment designed to answer important questions pertinent to that approach, all informing the ongoing development of future human studies by optimizing dose, schedule, biomarkers for inclusion/exclusion, and the thoughtful implementation of meaningful correlative studies.…”

Section: Feasibilitymentioning

confidence: 99%

Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

Roberts

Lizardo

Reed

et al. 2019

Cancer

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Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding. Cancer 2019;125:3514-3525.

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“…RecQ-like helicases are still to be established (Fan & Khanna 2015). Collectively, the proposal concerning the perceived contribution of the multiple-hit RecQ-like candidates to CTVT cellular phenotypes, is thereof originally specified by our theoretical analysis of variants listed in Decker set.…”

Section: Cellular Phenotypes Of Ctvt-recql4 and Ctvt-blm -Initial Conmentioning

confidence: 99%

Multiple mutations acquired into canine RecQ-like helicases encoded by the aneuploid genome of transmissible sarcoma

Wj¹

2018

Preprint

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Sticker sarcoma -a highly aneuploid, contagious neoplasm circulating in a domestic dog population -is broadly referred as a canine transmissible venereal tumour (CTVT). The karyotype of transmissible Sticker sarcoma appears as a collage of numerical and structural aberrations; the CTVT genome represents the generalized but stable neoplastic aneuploidy of monoclonal origins. Presented is an analysis of genetic events and variants underlying the aneuploid genomic structure of Sticker sarcoma described previously by Murchison et al. (2014) and Decker et al. (2015). Here we explored the above CTVT genomic compendia and mined the existing data -specifically looking for cases of convergence of multiple nonsynonymous variants onto a single gene -the mutational patterns indicative for Knudsonian 'two-hit' kinetics. A Table I is given, providing theoretical estimates of retaining the intact wild-type copy, expected as a function of a cumulative mutational convergence observed in unphased sequence consensus. We demonstrate that the two canine RecQ-like helicases: Bloom syndrome helicase and RECQL4, encoded by the aneuploid transmissible tumour, have accumulated a multitude of different mutations. Among the sets of most intensely mutated transmissible sarcoma genes, we also identified a canine FANCD2 -yet another previously unnoticed multiple-hit candidate factor. We discuss a possible role of mutated RecQ-like helicases and other cooperating factors, perceivably involved in the maintenance of the neoplastic aneuploidy. We suggest the proposed cooperative actions of CTVT RecQ-like DNA helicases could be relevant interpreting whether variants contributing to RecQ-dependent karyotypic traits, respond to selective pressures that preserve the aneuploid genomic structure of transmissible Sticker sarcoma.

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Comparative Aspects of Osteosarcoma Pathogenesis in Humans and Dogs

Cited by 42 publications

References 132 publications

A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma

A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma

Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

Multiple mutations acquired into canine RecQ-like helicases encoded by the aneuploid genome of transmissible sarcoma

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