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...ogs, with 65% of cases being homozygous [78]. is haplotype is within a region homologous to human chromosome 9p21 which is an important tumour suppressor locus and is implicated inmany human cancers =-=[79, 80]-=-. It is likely that the MTAP-CDKN2 locus is associated with more than one tumour type; Bernese mountain dogs are also susceptible to lymphoma, mast cell tumours, and osteosarcoma which seem to show fa...

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...ant tumour arising from blood vessels, probably less common than some of the other mesenchymalmalignancies, for example, �brosarcoma; it has been estimated to represent 7% of canine malignant tumours =-=[5]-=- and accounted for 24/100,000 dogs/year in one study [12], which is still considerably higher than angiosarcoma in humans [107]. e most common primary sites for hemangiosarcoma in dogs are visceral o...

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... in reduced genetic diversity within breeds and greater genetic divergence between breeds. e average nucleotide heterozygosity when considered across dog breeds is comparable to the human population =-=[29]-=-, but the level of genetic diversity within any single breed is considerably less than the species as a whole [25] indeed it has been estimated that whilst domestication of wild canid populations resu...

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... with mutations in BRCA1 where the risk of developing breast and ovarian cancer is greater in relatives of affected people, rather than the cancer being transmitted as an autosomal dominant condition =-=[45, 46]-=-. In contrast other breeds affected by a speci�c type of tumour may have a more speci�c genetic abnormality leading to that particular type of tumour. For example, renal cystadenocarcinoma and nodular...

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...1–21.4 10.75 German spitz/klein or mittel 43 7 16.3 5.2–27.3 11.33 Shih tzu 83 12 14.5 6.9–22.0 13.17 Other breeds (n = 93) 4524 806 17.8 Total 15,881 4282 27.0 which are equivalent to human diseases =-=[34, 35]-=-. e limited genetic diversity seen in purebred dogs, facilitates genetic linkage or association studies on relatively small populations as compared to humans [36, 37] and by using newly developed res...

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... and subungual variants are also described [168]. Canine melanocytic neoplasms vary widely in behavior; oral/mucosal forms are usuallymalignant and provide a good model for the human mucosal melanoma =-=[4]-=-, although a small proportion of tumours at this site are well differentiated and follow a more benign course [169]. Cutaneous and ocular tumours are usually benign, but tumours of the eyelid and nail...

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...ng (possibly resulting in microfractures) has been implicated in the aetiology of these tumours [83]. Increasing weight and height appear to be important predictive factors for the disease in the dog =-=[84]-=-. Growth hormone has been shown to be present in canine osteosarcoma samples [85] and studies evaluating the role of insulin-like growth factor1 (IGF-1) and its receptor IGF-1R and hepatocyte growth f...

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... normal times but in some breeds, for example, the Bernese mountain dog and the leonberger, genetic variation has been further reduced by serious population declines during war or hard economic times =-=[31]-=-. Mutations in a small number of genes of large effect are responsible for many breed characteristics; such selective breeding for exaggerated traits further reduces genetic diversity, and perhaps ris...

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...mour Adenoma Lipoma Histiocytoma Standardised incidence rate (/100,000 dogs/year) Mast cell tumour Soft tissue sarcoma Mammary carcinoma F 1: Incidence of speci�c types of canine neoplasia. From =-=[12]-=- (Pink bars denote malignant tumours, blue benign lesions). lymphoid, endocrine, alimentary, and oropharyngeal sites. Canine cutaneous histiocytoma was the most common tumour type overall with a stand...

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... aetiology of hemangiosarcoma in the breed. 5. Mast Cell Tumour Mast cell tumours (MCTs) are common tumours of the canine skin, estimated to represent 7–21 percent of all skin tumours in this species =-=[15, 129, 130]-=-. In the UK, MCT is the secondmost common caninemalignancy, aer so tissue sarcoma with an incidence of 129 per 100,000 insured dogs per year [12]. Cutaneous MCTs are typically solitary lesions but t...

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...k [22]. An ownerbased questionnaire conducted in the UK segregated breeds into “overrepresented,” “average” and “underrepresented” with respect to dying of cancer and showed the same trends (Table 2) =-=[23]-=-.ese population-based studies provide useful indicators of breeds at risk of cancer, but should not be regarded as completely de�nitive because the outcome oen depends on the breed prevalence within...

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...1–21.4 10.75 German spitz/klein or mittel 43 7 16.3 5.2–27.3 11.33 Shih tzu 83 12 14.5 6.9–22.0 13.17 Other breeds (n = 93) 4524 806 17.8 Total 15,881 4282 27.0 which are equivalent to human diseases =-=[34, 35]-=-. e limited genetic diversity seen in purebred dogs, facilitates genetic linkage or association studies on relatively small populations as compared to humans [36, 37] and by using newly developed res...

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... poorly differentiated, pleomorphic tumours shown to have an immunophenotype consistent with a myeloid dendritic antigen presenting cell origin: CD1+, CD4−, CD11c+, CD11d−, MHC II+, ICAM−1+, andy−1± =-=[50]-=-. As many of these reagents cannot be used on formalin �xed para�n embedded sections, vimentin, MHC II, and the cell surface marker CD18 have become the standard panel for identi�cation of histiocytic...

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...canine osteosarcoma. Breeds reported to be at increased risk of developing osteosarcoma include the doberman, German shepherd, golden retriever, great Dane, Irish setter, rottweiler and Saint Bernard =-=[88, 91, 92]-=-, large sight-hounds such as Irish wolound, Scottish deerhound and Borzoi [84], greyhound, rottweiler and great Dane [83] and Irish wolound, Saint Bernard, and Leonberger [93]. It may be argued that...

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... tumours is likely to be similar to that of human tumours [4–8]. A general comparison of the incidence of canine cancer with that of human cancer highlights some striking similarities and differences =-=[9]-=-. Breast cancer is the most common malignancy in women and the mammary gland is a common site for tumour development in bitches, although the risk is reduced in bitches spayed at a young age [10], dem...

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... Bernard were the �ve breeds of dog with the highest mortality from tumour-related death.eBernese, Irish wolound, and leonberger were the top three in a subsequent examination of the same data base =-=[21]-=-. Bernese mountain dogs, �at-coated retrievers, golden retriever, and rottweilers were in the top 5 breeds with over 20% of deaths due to cancer in Denmark [22]. An ownerbased questionnaire conducted ...

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...t are responsible for many breed characteristics; such selective breeding for exaggerated traits further reduces genetic diversity, and perhaps risks selection of mutations that predispose to disease =-=[25, 32, 33]-=-. Over 350 inherited disorders have been described in purebred dogs many of ISRN Veterinary Science 3 T 1: Proportional cancer-related mortality by breed. Based on data from [1], cancer accounted ...

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...mosome 5q12, corresponding to a gene encoding tumour-suppressor protein folliculin [48]. It was subsequently shown that the same gene ismutated in Birt-Hogg-Dube syndrome, a similar disease in humans =-=[49]-=-. For the purpose of this paper, breed associations will be considered by tumour type rather than by breed. 2. Histiocytic Sarcoma Histiocytic sarcoma is the current term used to describe a spectrum o...

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...cluding the P13/AKT, KRAS, PTEN WNT-beta catenin pathways and the MAPK cascade (Table 5). ese �ndings con�rm and support the value of canine mammary cancer as a model for human breast carcinogenesis =-=[7, 209]-=-. Althoughmammary tumours are one of the targets being studies by a European consortium of canine geneticists and clinicians (LUPA), no publications to date have reported differential gene expression ...

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...eterozygosity when considered across dog breeds is comparable to the human population [29], but the level of genetic diversity within any single breed is considerably less than the species as a whole =-=[25]-=- indeed it has been estimated that whilst domestication of wild canid populations resulted in a 5% loss of nucleotide diversity, breed formation caused a 35% loss [30]. In many breeds the effective po...

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...und from the Middle East, and tibetan Terrier, Lhasa Apso from china), a group of Mastiff-like breeds, a group re�ecting shared ancestral herding behaviour, and a group of huntingtype dogs (Figure 2) =-=[43]-=-. Most recently a neighbor-joining tree of domestic dogs showing the relationship among the various dog breeds has been constructed by genotyping 10 to 12 dogs for each of 80 breeds (Figure 3) [26]. B...

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...ogs under 25 kg body weight [84, 94]. Interestingly IGF1 and its associated regions are a major contributing locus in size diversity in dogs, accounting for about 50% of the genetic variation in size =-=[95]-=-. Osteosarcoma is particularly prevalent in retired racing Greyhounds, possibly implicating stress or trauma in the aetiology of the disease in this breed [83, 96]. A familial incidence has been obser...

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...osed to developing certain types of cancer (and conversely some breeds are at lesser risk) offers a unique opportunity to study and understand the geneticmechanisms underpinning cancer susceptibility =-=[39, 40]-=-. e purpose of this article is to review the current literature on predispositions to cancer in pedigree dogs, including the recent advances in knowledge throughmolecular genetic, cytogenetic, and ge...

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...IGF-1) and its receptor IGF-1R and hepatocyte growth factor (HGF) and its receptor c-Met in osteosarcoma cell lines and tissues have shown that these factors may contribute to the malignant phenotype =-=[86, 87]-=-. Sex hormones may also contribute to osteosarcoma riskwith intactmales and females being reported to be at increased risk [84]. However in the rottweiler neutering before 1 year of age appeared to in...

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...2) [43]. Most recently a neighbor-joining tree of domestic dogs showing the relationship among the various dog breeds has been constructed by genotyping 10 to 12 dogs for each of 80 breeds (Figure 3) =-=[26]-=-. Breeds that share either common behaviors or morphologic traits are grouped together on the basis of DNA analysis, indicating that they probably share common ancestors. In this context ISRN Veterina...

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...less than the species as a whole [25] indeed it has been estimated that whilst domestication of wild canid populations resulted in a 5% loss of nucleotide diversity, breed formation caused a 35% loss =-=[30]-=-. In many breeds the effective population size is very small even in normal times but in some breeds, for example, the Bernese mountain dog and the leonberger, genetic variation has been further reduc...

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...ypes of cancer; for example, the Belgian shepherd has been documented to be at higher risk of gastric carcinoma [41] and the Scottish deerhound has been shown to have a heritable risk of osteosarcoma =-=[42]-=-. Considering the genetic structure of the purebred dog, phylogenetic analysis has shown separation of several breeds with ancient origin from a large group of breeds with presumed European origins. ...

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...odular dermato�brosis (RCND) is a rare inherited cancer syndrome in German shepherd dogs. Affected dogs develop bilateral multifocal tumours in the kidneys and multiple dense collagenous skin nodules =-=[47]-=-. In the dog the disease gene was mapped to a region on canine chromosome 5q12, corresponding to a gene encoding tumour-suppressor protein folliculin [48]. It was subsequently shown that the same gene...

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... a whole, certain pedigree breeds appear predisposed to this disease, notably the Bernese mountain dog where the disseminated form of histiocytic sarcoma accounts for up to 25% of deaths in the breed =-=[57]-=- and the �at-coated retriever where the localised form is more common and accounts for approximately 25% of all tumours in the breed, and up to 50% of all malignancies [58, 59]. Disseminated histiocyt...

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...ffected [65]. Included in the visceral form affecting this breed is the hemophagocytic variant of histiocytic sarcoma, which arises from splenic or bone marrow derived macrophages and expresses CD11d =-=[69, 70]-=-. Furthermore localised periarticular histiocytic sarcoma is ISRN Veterinary Science 7 Basenji AkitasChow ChowsDingosShar-PeisAlaskan MalamutesSiberian HuskysAfghan houndsSalukisAmerican Eskimo dogsSa...

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...eight bearing, and rapid bone growth during early development along with bone stress due to weight bearing (possibly resulting in microfractures) has been implicated in the aetiology of these tumours =-=[83]-=-. Increasing weight and height appear to be important predictive factors for the disease in the dog [84]. Growth hormone has been shown to be present in canine osteosarcoma samples [85] and studies ev...

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...emale dogs [88]. As is the case inmany human and canine cancers, alterations in the function of the tumour suppressor genes RB and TP53 have been implicated in the pathogenesis of canine osteosarcoma =-=[89, 90]-=-. e fact that speci�c breeds appear predisposed suggests that more speci�c genetic factors may be implicated in the aetiology of canine osteosarcoma. Breeds reported to be at increased risk of develo...

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...hat canine osteosarcoma is a good clinical model for the human disease [97–99] and there is a growing body of evidence to show that canine and human osteosarcoma have a similar molecular pathogenesis =-=[100, 101]-=-. Gene expression pro�ling of canine osteosarcoma has revealed genes associated with progression, survival, and metastasis that are relevant to human osteosarcoma [100, 102–105]. As is the case in hum...

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.... 1. Introduction Cancer is an important disease in dogs and represents one of the major causes of canine death accounting for 27% of all deaths in purebred dogs in the UK in a recent mortality study =-=[1]-=-. is is slightly higher than what previously reported in a Danish Kennel club study (14.5% by Proschowesky et al.) and an earlier UK study (15.7% by Michell) but similar to a postmortem series of 200...

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...ease. In contrast, carcinomas of the prostate, a very common condition in men and also associated with hormonal stimulation, is relatively uncommon in dogs and occurs more frequently in neutered dogs =-=[11]-=-. Carcinomas of the lung and large bowel, the most common human tumours excluding breast and prostate, do not feature highly in the canine population, whereas so tissue sarcomas, which are rare in hu...

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...are equivalent to human diseases [34, 35]. e limited genetic diversity seen in purebred dogs, facilitates genetic linkage or association studies on relatively small populations as compared to humans =-=[36, 37]-=- and by using newly developed resources, genome wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders [38]. Although most forms of cancer are likel...

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...s and multiple dense collagenous skin nodules [47]. In the dog the disease gene was mapped to a region on canine chromosome 5q12, corresponding to a gene encoding tumour-suppressor protein folliculin =-=[48]-=-. It was subsequently shown that the same gene ismutated in Birt-Hogg-Dube syndrome, a similar disease in humans [49]. For the purpose of this paper, breed associations will be considered by tumour ty...

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...as been reported to be 49 days [64]. In �at-coated retrievers localised lesions most commonly develop in the deep musculature of the limbs or in periarticular sites; the elbow is the most common site =-=[65]-=-. Even these localised lesions are highly malignant with rapid dissemination to lymph nodes preceding haematogenous spread to parenchymal organs and the skin in over 70% of cases [66]. us both the lo...

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...ogs, with 65% of cases being homozygous [78]. is haplotype is within a region homologous to human chromosome 9p21 which is an important tumour suppressor locus and is implicated inmany human cancers =-=[79, 80]-=-. It is likely that the MTAP-CDKN2 locus is associated with more than one tumour type; Bernese mountain dogs are also susceptible to lymphoma, mast cell tumours, and osteosarcoma which seem to show fa...

Citation Context

...IGF-1) and its receptor IGF-1R and hepatocyte growth factor (HGF) and its receptor c-Met in osteosarcoma cell lines and tissues have shown that these factors may contribute to the malignant phenotype =-=[86, 87]-=-. Sex hormones may also contribute to osteosarcoma riskwith intactmales and females being reported to be at increased risk [84]. However in the rottweiler neutering before 1 year of age appeared to in...

Citation Context

...ith intactmales and females being reported to be at increased risk [84]. However in the rottweiler neutering before 1 year of age appeared to increase risk of bone sarcoma in bothmale and female dogs =-=[88]-=-. As is the case inmany human and canine cancers, alterations in the function of the tumour suppressor genes RB and TP53 have been implicated in the pathogenesis of canine osteosarcoma [89, 90]. e fa...

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...canine osteosarcoma. Breeds reported to be at increased risk of developing osteosarcoma include the doberman, German shepherd, golden retriever, great Dane, Irish setter, rottweiler and Saint Bernard =-=[88, 91, 92]-=-, large sight-hounds such as Irish wolound, Scottish deerhound and Borzoi [84], greyhound, rottweiler and great Dane [83] and Irish wolound, Saint Bernard, and Leonberger [93]. It may be argued that...

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... Saint Bernard [88, 91, 92], large sight-hounds such as Irish wolound, Scottish deerhound and Borzoi [84], greyhound, rottweiler and great Dane [83] and Irish wolound, Saint Bernard, and Leonberger =-=[93]-=-. It may be argued that these predispositions may be related to size rather than breed, and this is supported by the fact that greyhounds and whippets consistently clustered together in an analysis of...

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...of factors may contribute to an increase in the diagnosis of cancer in dogs; as a result of improvements in health and welfare animals are living longer and cancer is generally a disease of older age =-=[3]-=-. Advances in veterinary medicine, particularly diagnostics and higher expectations of the pet owning public, are likely to result in an increased rate of diagnosis. As is the case in the human popula...

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...ences [9]. Breast cancer is the most common malignancy in women and the mammary gland is a common site for tumour development in bitches, although the risk is reduced in bitches spayed at a young age =-=[10]-=-, demonstrating the importance of endogenous hormones in the development of this disease. In contrast, carcinomas of the prostate, a very common condition in men and also associated with hormonal stim...

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...reed has been shown to play a role in the epidemiology of lymphoma with several studies showing a signi�cantly higher relative risk for boxers, bullmastiff and bulldog breeds compared to other breeds =-=[9, 14, 154, 155]-=-. Other breeds identi�ed with increased relative risk include basset hound, St Bernard, Scottish terrier, Airedale terrier, Bouvier des Flandres, Labrador retriever, and rottweiler [14, 156]. Familial...

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...ttweiler, Italian spinone, leonberger, Staffordshire bull terrier, Welsh terrier, and giant Schnauzer ([1], Table 1). In a study of rates and causes of death in insured dogs in Sweden, Bonnett et al. =-=[16]-=- found that the Bernese mountain dog, Irish wolound, �at-coated retriever, boxer, and Saint Bernard were the �ve breeds of dog with the highest mortality from tumour-related death.eBernese, Irish wo...

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...hat contribute to the pathogenesis of the disease. 8. Mammary Tumours Tumours of the mammary glands are the most common tumour to affect entire bitches representing between 50−70% of all tumour types =-=[18, 195]-=-. A standardised incidence rate of 205/100,000 dogs/year has been reported in a population of insured dogs in theUK [12] and in a Swedish study of insured dogs that the overall rate of mammary tumour ...

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...quent examination of the same data base [21]. Bernese mountain dogs, �at-coated retrievers, golden retriever, and rottweilers were in the top 5 breeds with over 20% of deaths due to cancer in Denmark =-=[22]-=-. An ownerbased questionnaire conducted in the UK segregated breeds into “overrepresented,” “average” and “underrepresented” with respect to dying of cancer and showed the same trends (Table 2) [23]....

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... is amajor confounding factor: for example the reason the bulldog has an apparent low risk of cancer in Table 1 may be due to its short lifeexpectancy due to other health issues that affect the breed =-=[24]-=-. Other limitations of such studies include owner compliance, bias through nonrandom sampling of the pedigree dog population, and accuracy of owner-reported cause of death. Furthermore a small number ...

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...st be registered as well. is combined with the frequent use of popular sires and inbreeding practices means that each breed is a closed, isolated population with virtually no gene �ow between breeds =-=[28]-=-. Over the past 200 years this practice has resulted in reduced genetic diversity within breeds and greater genetic divergence between breeds. e average nucleotide heterozygosity when considered acro...

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...t are responsible for many breed characteristics; such selective breeding for exaggerated traits further reduces genetic diversity, and perhaps risks selection of mutations that predispose to disease =-=[25, 32, 33]-=-. Over 350 inherited disorders have been described in purebred dogs many of ISRN Veterinary Science 3 T 1: Proportional cancer-related mortality by breed. Based on data from [1], cancer accounted ...

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...are equivalent to human diseases [34, 35]. e limited genetic diversity seen in purebred dogs, facilitates genetic linkage or association studies on relatively small populations as compared to humans =-=[36, 37]-=- and by using newly developed resources, genome wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders [38]. Although most forms of cancer are likel...

Citation Context

...ll populations as compared to humans [36, 37] and by using newly developed resources, genome wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders =-=[38]-=-. Although most forms of cancer are likely multifactorial in aetiology, the fact that different breeds of dog are predisposed to developing certain types of cancer (and conversely some breeds are at l...

Citation Context

...osed to developing certain types of cancer (and conversely some breeds are at lesser risk) offers a unique opportunity to study and understand the geneticmechanisms underpinning cancer susceptibility =-=[39, 40]-=-. e purpose of this article is to review the current literature on predispositions to cancer in pedigree dogs, including the recent advances in knowledge throughmolecular genetic, cytogenetic, and ge...

Citation Context

...ed risk, although that is not to say that these latter breeds do not suffer particular types of cancer; for example, the Belgian shepherd has been documented to be at higher risk of gastric carcinoma =-=[41]-=- and the Scottish deerhound has been shown to have a heritable risk of osteosarcoma [42]. Considering the genetic structure of the purebred dog, phylogenetic analysis has shown separation of several b...

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...gesting that some breeds may be like the rare human LiFraumeni families where a germ line mutation in a tumour suppressor gene (TP53) results in a hereditary predisposition to several types of cancer =-=[44]-=- or they may resemble the situation in families with mutations in BRCA1 where the risk of developing breast and ovarian cancer is greater in relatives of affected people, rather than the cancer being ...

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... with mutations in BRCA1 where the risk of developing breast and ovarian cancer is greater in relatives of affected people, rather than the cancer being transmitted as an autosomal dominant condition =-=[45, 46]-=-. In contrast other breeds affected by a speci�c type of tumour may have a more speci�c genetic abnormality leading to that particular type of tumour. For example, renal cystadenocarcinoma and nodular...

Citation Context

... of these reagents cannot be used on formalin �xed para�n embedded sections, vimentin, MHC II, and the cell surface marker CD18 have become the standard panel for identi�cation of histiocytic sarcoma =-=[51, 52]-=-. Localised histiocytic sarcoma describes those lesions which present as solitary masses, previously referred to as malignant �brous histiocytoma [53–56], and disseminated histiocytic sarcoma, those t...

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... of these reagents cannot be used on formalin �xed para�n embedded sections, vimentin, MHC II, and the cell surface marker CD18 have become the standard panel for identi�cation of histiocytic sarcoma =-=[51, 52]-=-. Localised histiocytic sarcoma describes those lesions which present as solitary masses, previously referred to as malignant �brous histiocytoma [53–56], and disseminated histiocytic sarcoma, those t...

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... 25% of deaths in the breed [57] and the �at-coated retriever where the localised form is more common and accounts for approximately 25% of all tumours in the breed, and up to 50% of all malignancies =-=[58, 59]-=-. Disseminated histiocytic sarcoma in the Bernese typically presents with vague clinical signs including lethargy, anorexia, and weight loss. Investigations revealmultifocal disease primarily affectin...

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... 25% of deaths in the breed [57] and the �at-coated retriever where the localised form is more common and accounts for approximately 25% of all tumours in the breed, and up to 50% of all malignancies =-=[58, 59]-=-. Disseminated histiocytic sarcoma in the Bernese typically presents with vague clinical signs including lethargy, anorexia, and weight loss. Investigations revealmultifocal disease primarily affectin...

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...ding anemia and thrombocytopenia are common [60–63]. e disease is rapidly progressive and fatal; many dogs are euthanized upon diagnosis; survival time from diagnosis has been reported to be 49 days =-=[64]-=-. In �at-coated retrievers localised lesions most commonly develop in the deep musculature of the limbs or in periarticular sites; the elbow is the most common site [65]. Even these localised lesions ...

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...most common site [65]. Even these localised lesions are highly malignant with rapid dissemination to lymph nodes preceding haematogenous spread to parenchymal organs and the skin in over 70% of cases =-=[66]-=-. us both the localised and disseminated forms of histiocytic sarcoma are highly malignant conditions that are largely refractory to conventional treatments and carry a very poor prognosis. Treatment...

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...ffected [65]. Included in the visceral form affecting this breed is the hemophagocytic variant of histiocytic sarcoma, which arises from splenic or bone marrow derived macrophages and expresses CD11d =-=[69, 70]-=-. Furthermore localised periarticular histiocytic sarcoma is ISRN Veterinary Science 7 Basenji AkitasChow ChowsDingosShar-PeisAlaskan MalamutesSiberian HuskysAfghan houndsSalukisAmerican Eskimo dogsSa...

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...is, indicating that they probably share common ancestors. e colours indicate breeds that probably share common founders. also recognised in the BMD, where it is possibly predisposed by joint disease =-=[71]-=-. Histiocytic sarcoma is not exclusive to the Bernese and �at-coated retriever� other breeds of dog where histiocytic sarcoma has been reported with some frequency include rottweilers and golden retri...

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...ese breeds of dog suggests a heritable predisposition. A recent study of Danish Bernese mountain dogs described 13 dogs diagnosed with malignant histiocytosis, of which 11 were genealogically related =-=[76]-=-. In 1995 Padgett analysed the inheritance of “histiocytosis” in 127 affected Bernese mountain dogs and suggested a polygenic mode of inheritance and a calculated heritability of 0.298 [57]. More rece...

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...d that an oligogenic model was likely to be a better description of the genetic model underlying the disease [64]. Histiocytic sarcoma has recently been investigated by molecular cytogenetic pro�ling =-=[77]-=- and genome wide association studies [78]. Using genome wide array comparative genomic hybridization, supplemented with �uorescence in situ hybridization and loss of heterozygosity analysis, copy numb...

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...be a better description of the genetic model underlying the disease [64]. Histiocytic sarcoma has recently been investigated by molecular cytogenetic pro�ling [77] and genome wide association studies =-=[78]-=-. Using genome wide array comparative genomic hybridization, supplemented with �uorescence in situ hybridization and loss of heterozygosity analysis, copy number aberrations (CNAs) were assessed in 14...

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...ortant in other canine sarcomas. Disruption of chromosome 11 involving the loss of the CDKN2b-CDKN2a tumour suppressor gene cluster region has been reported in two �brosarcomas in Labrador retrievers =-=[81]-=-. e same study sequenced exon 1 of CDKN2B using DNA from blood of 141 dogs of 18 different breeds and showed widespread polymorphism of this �rst exon. Seven alleles were recorded and sixteen of the ...

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...umour of bone in dogs accounting for 85 −90% of primary bone tumours and almost exclusively affects the large and giant breeds such as rottweiler, great Dane, Irish wolound, greyhound, Saint Bernard =-=[82]-=-. e aetiology of osteosarcoma is probably multifactorial; the predilection for the tumour to develop at metaphyseal region of long bones, especially the distal radius and proximal humerus, correlates...

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... these tumours [83]. Increasing weight and height appear to be important predictive factors for the disease in the dog [84]. Growth hormone has been shown to be present in canine osteosarcoma samples =-=[85]-=- and studies evaluating the role of insulin-like growth factor1 (IGF-1) and its receptor IGF-1R and hepatocyte growth factor (HGF) and its receptor c-Met in osteosarcoma cell lines and tissues have sh...

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...analysis of molecular variance inmicrosatellite loci [26, 43], yet whilst appendicular osteosarcoma affects greyhounds [82], the disease is rare in whippets, or indeed in dogs under 25 kg body weight =-=[84, 94]-=-. Interestingly IGF1 and its associated regions are a major contributing locus in size diversity in dogs, accounting for about 50% of the genetic variation in size [95]. Osteosarcoma is particularly p...

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...out 50% of the genetic variation in size [95]. Osteosarcoma is particularly prevalent in retired racing Greyhounds, possibly implicating stress or trauma in the aetiology of the disease in this breed =-=[83, 96]-=-. A familial incidence has been observed in Saint Bernards [91] and more recently a study modelling the transmission of osteosarcoma in a population of over 1000 Scottish deerhounds estimated heritabi...

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...hat canine osteosarcoma is a good clinical model for the human disease [97–99] and there is a growing body of evidence to show that canine and human osteosarcoma have a similar molecular pathogenesis =-=[100, 101]-=-. Gene expression pro�ling of canine osteosarcoma has revealed genes associated with progression, survival, and metastasis that are relevant to human osteosarcoma [100, 102–105]. As is the case in hum...