| 1. |
- Thomas, Rachael, et al.
(författare)
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Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma
- 2014
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Ingår i: Chromosome Research. - : Springer Science and Business Media LLC. - 0967-3849 .- 1573-6849. ; 22:3, s. 305-319
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Tidskriftsartikel (refereegranskat)abstract
- Canine hemangiosarcoma is a highly aggressive vascular neoplasm associated with extensive clinical and anatomical heterogeneity and a grave prognosis. Comprehensive molecular characterization of hemangiosarcoma may identify novel therapeutic targets and advanced clinical management strategies, but there are no published reports of tumor-associated genome instability and disrupted gene dosage in this cancer. We performed genome-wide microarray-based somatic DNA copy number profiling of 75 primary intra-abdominal hemangiosarcomas from five popular dog breeds that are highly predisposed to this disease. The cohort exhibited limited global genomic instability, compared to other canine sarcomas studied to date, and DNA copy number aberrations (CNAs) were predominantly of low amplitude. Recurrent imbalances of several key cancer-associated genes were evident; however, the global penetrance of any single CNA was low and no distinct hallmark aberrations were evident. Copy number gains of dog chromosomes 13, 24, and 31, and loss of chromosome 16, were the most recurrent CNAs involving large chromosome regions, but their relative distribution within and between cases suggests they most likely represent passenger aberrations. CNAs involving CDKN2A, VEGFA, and the SKI oncogene were identified as potential driver aberrations of hemangiosarcoma development, highlighting potential targets for therapeutic modulation. CNA profiles were broadly conserved between the five breeds, although subregional variation was evident, including a near twofold lower incidence of VEGFA gain in Golden Retrievers versus other breeds (22 versus 40 %). These observations support prior transcriptional studies suggesting that the clinical heterogeneity of this cancer may reflect the existence of multiple, molecularly distinct subtypes of canine hemangiosarcoma.
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| 2. |
- Thomas, Rachael, et al.
(författare)
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Refining tumor-associated aneuploidy through 'genomic recoding' of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas
- 2011
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 52:7, s. 1321-1335
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Tidskriftsartikel (refereegranskat)abstract
- Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. 'Genomic recoding' of canine NHL data into a 'virtual human' chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.
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