Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating precision medicine (PMed) trials

ABSTRACT: Feasibility trial to examine the ability to conduct molecular guided therapy in a geographically distributed systems within strict time constraints Canine patients were enrolled across a broad panel of tumor types where tumor samples were acquired and processed to preserve RNA quality for genomic analysis at distributed locations to predict possible effective therapies. Genomic driven therapy suggestion derived using a collection of algorithms based on tumor expression levels.

ORGANISM(S): Canis lupus

SUBMITTER: David Cherba

PROVIDER: E-GEOD-51131 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

Paoloni Melissa M Webb Craig C Mazcko Christina C Cherba David D Hendricks William W Lana Susan S Ehrhart E J EJ Charles Brad B Fehling Heather H Kumar Leena L Vail David D Henson Michael M Childress Michael M Kitchell Barbara B Kingsley Christopher C Kim Seungchan S Neff Mark M Davis Barbara B Khanna Chand C Trent Jeffrey J

PloS one 20140317 3

<h4>Background</h4>Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize ...[more]

PMID: 24637659

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Project description:Transcriptional profiling of Control and RbpjkCNULL lungs from E18.5. For microarray profiling, total RNA from E18.5 lungs was submitted for labeling and hybridization (Mouse Gene 1.0 ST Whole Genome Array, Affymetrix) to the Boston University Microarray Core facility. Clara cells (CCs) are a morphologically and operationally heterogeneous population of secretoglobin Scgb1a1-expressing secretory cells crucial for airway homeostasis and post-injury repair. Insights into the extent and origin of CC diversity have been hindered by the limited knowledge of markers of these cells and their precursors. To identify novel putative markers of CCs we characterized global changes in gene expression in embryonic lungs in which CCs were suppressed by conditional disruption of Notch signaling (Rbpjkcnull). Microarray profiling and Real Time PCR (qRT-PCR) identified eleven genes differentially downregulated in the E18.5 airways of Rbpjkcnull compared to controls, nearly half not previously known to mark CCs. Remarkably, in situ hybridization (ISH) revealed overlapping but also distinct domains of expression of these genes in E18.5 controls. Notably, Reg3g, Chad, Gabrp and Lrrc26 were selectively expressed in CCs of proximal airways and Upk3a expression was highly enriched in a CC subpopulation surrounding Neuroepithelial Bodies (NEBs). All genes expressed in the adult airways were found to be expressed in adult CCs and downregulated by selective CC ablation in a Naphthalene model of injury. Flow cytometry-based isolation of CCs from different airway regions of adult B1-EGFP reporter mice and qRT-PCR corroborated the spatial enrichment in gene expression observed by ISH. Remarkably, although, Scgb3a2, Upk3a, Cyp2f2, Cbr2, Krt15 could be detected unambiguously in airway progenitors as early as E14.5, only Scgb3a2 and Upk3a had their expression suppressed by disruption of Notch signaling, implicating both genes as the earliest markers for CC differentiation. Our study supports the idea that the diversification of the CC phenotype already arises during embryonic development and identifies candidate markers that can be used to investigate this process. Control (n=3) versus RbpjkCNULL(n=3)

Dataset Information

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating precision medicine (PMed) trials

Publications

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

Similar Datasets

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