Canine Genetics Offers New Mechanisms for the Study of Human Cancer

Cadieu, Édouard; Ostrander, Elaine A.

doi:10.1158/1055-9965.epi-07-2667

Cited by 33 publications

(34 citation statements)

References 37 publications

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“…As discussed in §2, canine cancers share evolutionarily conserved genomic changes that are found in their human counterparts. Man's best friend is already providing scientists with an opportunity to generate data beneficial to both species [3,4,10,11,18,19].…”

Section: (A) On the Origin Of Dogs (And Their Cancer Risk)mentioning

confidence: 99%

Comparative oncology: what dogs and other species can teach us about humans with cancer

Schiffman

Breen

2015

Phil. Trans. R. Soc. B

316

315

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One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'. Over 1.66 million humans (approx. 500/100 000 population rate) and over 4.2 million dogs (approx. 5300/100 000 population rate) are diagnosed with cancer annually in the USA. The interdisciplinary field of comparative oncology offers a unique and strong opportunity to learn more about universal cancer risk and development through epidemiology, genetic and genomic investigations. Working across species, researchers from human and veterinary medicine can combine scientific findings to understand more quickly the origins of cancer and translate these findings to novel therapies to benefit both human and animals. This review begins with the genetic origins of canines and their advantage in cancer research. We next focus on recent findings in comparative oncology related to inherited, or genetic, risk for tumour development. We then detail the somatic, or genomic, changes within tumours and the similarities between species. The shared cancers between humans and dogs that we discuss include sarcoma (osteosarcoma, soft tissue sarcoma, histiocytic sarcoma, hemangiosarcoma), haematological malignancies (lymphoma, leukaemia), bladder cancer, intracranial neoplasms (meningioma, glioma) and melanoma. Tumour risk in other animal species is also briefly discussed. As the field of genomics advances, we predict that comparative oncology will continue to benefit both humans and the animals that live among us.

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Section: (A) On the Origin Of Dogs (And Their Cancer Risk)mentioning

confidence: 99%

Comparative oncology: what dogs and other species can teach us about humans with cancer

Schiffman

Breen

2015

Phil. Trans. R. Soc. B

316

315

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“…This is true not only in human populations but also in the domestic dog, where approximately 25% of the population will develop cancer in their lifetime and, like humans, the incidence increases rapidly with age (2,3). Many naturally occurring cancers in domestic dogs closely mimic their human counterparts in both histopathological features and biological behavior, including distant metastasis, response to therapy, and extensive intratumor heterogeneity (4–6). Breed-specific risk paired with the simplified canine genetic architecture has enabled identification of susceptibility loci for several malignancies including renal cell carcinoma, histiocytic sarcoma, osteosarcoma, and squamous cell carcinoma of the digit (7–10).…”

Section: Introductionmentioning

confidence: 99%

Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer—Evidence for a Relevant Model System and Urine-Based Diagnostic Test

Decker

Parker

Dhawan

et al. 2015

Molecular Cancer Research

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125

155

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Targeted cancer therapies offer great clinical promise, but treatment resistance is common, and basic research aimed at overcoming this challenge is limited by reduced genomic and biological complexity in artificially induced rodent tumors compared to their human counterparts. Animal models that more faithfully recapitulate genotype-specific human pathology could improve the predictive value of these investigations. Here, a newly identified animal model for oncogenic BRAF-driven cancers is described. With 20,000 new cases in the United States each year, canine invasive transitional cell carcinoma of the bladder (InvTCC) is a common, naturally occurring malignancy that shares significant histological, biological, and clinical phenotypes with human muscle invasive bladder cancer. In order to identify somatic drivers of canine InvTCC, the complete transcriptome for multiple tumors was determined by RNAseq. All tumors harbored a somatic mutation that is homologous to the human BRAF(V600E) mutation, and an identical mutation was present in 87% of 62 additional canine InvTCC tumors. The mutation was also detectable in the urine sediments of all dogs tested with mutation-positive tumors. Functional experiments suggest that, like human tumors, canine activating BRAF mutations potently stimulate the mitogen activated protein kinase (MAPK) pathway. Cell lines with the mutation have elevated levels of phosphorylated MEK, compared to a line with wild type BRAF. This effect can be diminished through application of the BRAF(V600E) inhibitor vemurafenib. These findings set the stage for canine InvTCC as a powerful system to evaluate BRAF-targeted therapies, as well as therapies designed to overcome resistance, which could enhance treatment of both human and canine cancers

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“…However, only one female (canine 22) had this tality of women as a result of mammary tumors. In this study, two similarities of canine IELs with the equivalent developmental stage in female breast cancer are proposed: 1) The origin of carcinomas in canines resembles that of human mammary carcinomas as described by the "sick lobe" theory [11], and 2) Consistent with human early CIS [28,67,73,75], more frequent multifocal ruptures of the myoepithelial layer were observed in canine CIS.…”

Section: Discussionmentioning

confidence: 81%

“…However, comparative studies of these carcinomas during the first developmental stages have received less attention [10,73,74]. The detection of early lesions in MG has demonstrated its importance for preventing and diminishing the mor-that within the same MG there is substantial heterogeneity and that the benign and malignant lesions are multifocal and have variable size, they did not interpret the meaning of these findings.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2017

Int J Pathol Clin Res

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Canine Genetics Offers New Mechanisms for the Study of Human Cancer

Cited by 33 publications

References 37 publications

Comparative oncology: what dogs and other species can teach us about humans with cancer

Comparative oncology: what dogs and other species can teach us about humans with cancer

Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer—Evidence for a Relevant Model System and Urine-Based Diagnostic Test

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