Isolation and chromosomal assignment of canine genomic BAC clones representing 25 cancer-related genes

Thomas, Rachael; Bridge, Wendy L; Benke, Kálmán; Breen, Matthew

doi:10.1159/000075757

Cited by 17 publications

(9 citation statements)

References 25 publications

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“…Tumor T47 carried an additional copy of chromosome CFA1. Gains of CFA1 were also detected in studies of other dog cancers [71], [72] and the proto-oncogene MYB has been mapped to this chromosome [73]. MYB amplification has been found at high frequencies in human hereditary breast cancer.…”

Section: Discussionmentioning

confidence: 88%

Genome Aberrations in Canine Mammary Carcinomas and Their Detection in Cell-Free Plasma DNA

Beck¹,

Hennecke

Bornemann-Kolatzki³

et al. 2013

PLoS ONE

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Mammary tumors are the most frequent cancers in female dogs exhibiting a variety of histopathological differences. There is lack of knowledge about the genomes of these common dog tumors. Five tumors of three different histological subtypes were evaluated. Massive parallel sequencing (MPS) was performed in comparison to the respective somatic genome of each animal. Copy number and structural aberrations were validated using droplet digital PCR (ddPCR). Using mate-pair sequencing chromosomal aneuploidies were found in two tumors, frequent smaller deletions were found in one, inter-chromosomal fusions in one other, whereas one tumor was almost normal. These aberrations affect several known cancer associated genes such as cMYC, and KIT. One common deletion of the proximal end of CFA27, harboring the tumor suppressor gene PFDN5 was detected in four tumors. Using ddPCR, this deletion was validated and detected in 50% of tumors (N = 20). Breakpoint specific dPCRs were established for four tumors and tumor specific cell-free DNA (cfDNA) was detected in the plasma. In one animal tumor-specific cfDNA was found >1 year after surgery, attributable to a lung metastasis. Paired-end sequencing proved that copy-number imbalances of the tumor are reflected by the cfDNA. This report on chromosomal instability of canine mammary cancers reveals similarities to human breast cancers as well as special canine alterations. This animal model provides a framework for using MPS for screening for individual cancer biomarkers with cost effective confirmation and monitoring using ddPCR. The possibility exists that ddPCR can be expanded to screening for common cancer related variants.

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Section: Discussionmentioning

confidence: 88%

Genome Aberrations in Canine Mammary Carcinomas and Their Detection in Cell-Free Plasma DNA

Beck¹,

Hennecke

Bornemann-Kolatzki³

et al. 2013

PLoS ONE

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“…If deletion of 13q14 were evolutionarily conserved in the dog, it would manifest as a deletion within CFA 22q11.2 (Thomas et al 2003a) (Figure 4a). To explore this, we initially performed multicolor FISH on metaphase preparations from a case of canine CLL (Figure 4b), using a selection of seven BAC clones that spanned the full length of CFA 22 (Breen et al 2004) including a clone containing the RB1 locus (RPCI-81 312-b24) (Thomas et al 2003a). Differential spectral labeling of these BACs revealed clearly a hemizygous deletion of the RB1 locus (Figure 4c).…”

Section: Deletion Of the Rb-1 Locus In Canine Cllmentioning

confidence: 99%

Evolutionarily conserved cytogenetic changes in hematological malignancies of dogs and humans – man and his best friend share more than companionship

2008

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The pathophysiological similarities shared by many forms of human and canine disease, combined with the sophisticated genomic resources now available for the dog, have placed 'man's best friend' in a position of high visibility as a model system for a variety of biomedical concerns, including cancer. The importance of nonrandom cytogenetic abnormalities in human leukemia and lymphoma was recognized over 40 years ago, but the mechanisms of genome reorganization remain incompletely understood. The development of molecular cytogenetics, using fluorescence in situ hybridization (FISH) technology, has played a significant role in our understanding of cancer biology by providing a means for 'interrogating' tumor cells for a variety of gross genetic changes in the form of either numerical or structural chromosome aberrations. Here, we have identified cytogenetic abnormalities in naturally occurring canine hematopoietic tumors that are evolutionarily conserved compared with those that are considered characteristic of the corresponding human condition. These data suggest that humans and dogs share an ancestrally retained pathogenetic basis for cancer and that cytogenetic evaluation of canine tumors may provide greater insight into the biology of tumorigenesis.

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“…Of these, 87 were present on our first generation canine genomic microarray, among which are 26 clones containing canine orthologs of human cancer-related genes (Thomas et al 2003c). Three CFA Y clones have been reported elsewhere (Bannasch et al 2005).…”

Section: Selection Of Bac Clones For Microarray Generationmentioning

confidence: 99%

Construction of a 2-Mb resolution BAC microarray for CGH analysis of canine tumors

et al. 2005

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Recognition of the domestic dog as a model for the comparative study of human genetic traits has led to major advances in canine genomics. The pathophysiological similarities shared between many human and dog diseases extend to a range of cancers. Human tumors frequently display recurrent chromosome aberrations, many of which are hallmarks of particular tumor subtypes. Using a range of molecular cytogenetic techniques we have generated evidence indicating that this is also true of canine tumors. Detailed knowledge of these genomic abnormalities has the potential to aid diagnosis, prognosis, and the selection of appropriate therapy in both species. We recently improved the efficiency and resolution of canine cancer cytogenetics studies by developing a small-scale genomic microarray comprising a panel of canine BAC clones representing subgenomic regions of particular interest. We have now extended these studies to generate a comprehensive canine comparative genomic hybridization (CGH) array that comprises 1158 canine BAC clones ordered throughout the genome with an average interval of 2 Mb. Most of the clones (84.3%) have been assigned to a precise cytogenetic location by fluorescence in situ hybridization (FISH), and 98.5% are also directly anchored within the current canine genome assembly, permitting direct translation from cytogenetic aberration to DNA sequence. We are now using this resource routinely for high-throughput array CGH and single-locus probe analysis of a range of canine cancers. Here we provide examples of the varied applications of this resource to tumor cytogenetics, in combination with other molecular cytogenetic techniques.

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Isolation and chromosomal assignment of canine genomic BAC clones representing 25 cancer-related genes

Cited by 17 publications

References 25 publications

Genome Aberrations in Canine Mammary Carcinomas and Their Detection in Cell-Free Plasma DNA

Genome Aberrations in Canine Mammary Carcinomas and Their Detection in Cell-Free Plasma DNA

Evolutionarily conserved cytogenetic changes in hematological malignancies of dogs and humans – man and his best friend share more than companionship

Construction of a 2-Mb resolution BAC microarray for CGH analysis of canine tumors

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