Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer


ABSTRACT: Well-defined, closed breeding populations coupled with excessive disease predispositions among purebred domestic dog breeds offer unique advantages to genetic studies of disease susceptibility. Advantages offered by canine population substructure, combined with similarity to human disease in terms of clinical presentation and response to treatment, make the dog a particularly attractive system for finding genes associated with cancer. Cancers that have been difficult to study in human families or populations are of particular interest, especially those associated with one or a small number of breeds and a high level of occurrence. Histiocytic sarcoma (HS) is a rare and poorly understood neoplasm in humans, however it occurs in 15-25% of Bernese Mountain Dogs (BMD). By combining genome-wide association studies from two geographic populations of BMD followed by fine mapping and sequencing, we have identified a cancer-associated haplotype within the MTAP/CDKN2A locus that is present in 95% of all affected BMD. The haplotype is within the region homologous to human chromosome 9p21, which has been implicated in numerous complex genetic diseases including several cancers. These results demonstrate the power of studying distinctive malignancies in highly predisposed dog breeds. Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight regarding this cancer-associated, complex, and yet poorly understood genomic region. Genomic DNA was collected from affected and unaffected BMD in North America (NA) and Europe. Both independent and combined genome-wide association studies (GWAS) were used to identify cancer-associated loci.

ORGANISM(S): Canis lupus familiaris

SUBMITTER: Heidi Parker 

PROVIDER: E-GEOD-38011 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The MTAP-CDKN2A locus confers susceptibility to a naturally occurring canine cancer.

Shearin Abigail L AL   Hedan Benoit B   Cadieu Edouard E   Erich Suzanne A SA   Schmidt Emmett V EV   Faden Daniel L DL   Cullen John J   Abadie Jerome J   Kwon Erika M EM   Gröne Andrea A   Devauchelle Patrick P   Rimbault Maud M   Karyadi Danielle M DM   Lynch Mary M   Galibert Francis F   Breen Matthew M   Rutteman Gerard R GR   André Catherine C   Parker Heidi G HG   Ostrander Elaine A EA  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20120523 7


<h4>Background</h4>Advantages offered by canine population substructure, combined with clinical presentations similar to human disorders, makes the dog an attractive system for studies of cancer genetics. Cancers that have been difficult to study in human families or populations are of particular interest. Histiocytic sarcoma is a rare and poorly understood neoplasm in humans that occurs in 15% to 25% of Bernese Mountain Dogs (BMD).<h4>Methods</h4>Genomic DNA was collected from affected and unaf  ...[more]

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