Project description:Data underlying Sander et al., Oncogene 2005, June 20, Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model. Includes both array CGH and expression data.
Project description:Data underlying Sander et al., Oncogene 2005, June 20, Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model. Includes both array CGH and expression data. Abstract: Microarray-based formats offer a high-resolution alternative to conventional, chromosome-based comparative genomic hybridization (CGH) methods for assessing DNA copy number alteration (CNA) genome-wide in human cancer. For murine tumors, array CGH should provide even greater advantage, since murine chromosomes are more difficult to individually discern. We report here the adaptation and evaluation of a cDNA microarray-based CGH method for the routine characterization of CNAs in murine tumors, using mouse cDNA microarrays representing approximately 14,000 different genes, thereby providing an average mapping resolution of 109 kb. As a first application, we have characterized CNAs in a set of 10 primary and recurrent lymphomas derived from a Myc-induced murine lymphoma model. In primary lymphomas and more commonly in Myc-independent relapses, we identified a recurrent genomic DNA loss at chromosome 3G3-3H4, and recurrent amplifications at chromosome 3F2.1-3G3 and chromosome 15E1/E2-15F3, the boundaries of which we defined with high resolution. Further, by profiling gene expression using the same microarray platform, we identified within CNAs the relevant subset of candidate cancer genes displaying comparably altered expression, including Mcl1 (myeloid cell leukemia sequence 1), a highly expressed antiapoptotic gene residing within the chr 3 amplicon peak. CGH on mouse cDNA microarrays therefore represents a reliable method for the high-resolution characterization of CNAs in murine tumors, and a powerful approach for elucidating the molecular events in tumor development and progression in murine models. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design, arrayCGH, expression profiling
Project description:Data underlying Sander et al., Oncogene 2005, June 20, Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model. Includes both array CGH and expression data. Abstract: Microarray-based formats offer a high-resolution alternative to conventional, chromosome-based comparative genomic hybridization (CGH) methods for assessing DNA copy number alteration (CNA) genome-wide in human cancer. For murine tumors, array CGH should provide even greater advantage, since murine chromosomes are more difficult to individually discern. We report here the adaptation and evaluation of a cDNA microarray-based CGH method for the routine characterization of CNAs in murine tumors, using mouse cDNA microarrays representing approximately 14,000 different genes, thereby providing an average mapping resolution of 109 kb. As a first application, we have characterized CNAs in a set of 10 primary and recurrent lymphomas derived from a Myc-induced murine lymphoma model. In primary lymphomas and more commonly in Myc-independent relapses, we identified a recurrent genomic DNA loss at chromosome 3G3-3H4, and recurrent amplifications at chromosome 3F2.1-3G3 and chromosome 15E1/E2-15F3, the boundaries of which we defined with high resolution. Further, by profiling gene expression using the same microarray platform, we identified within CNAs the relevant subset of candidate cancer genes displaying comparably altered expression, including Mcl1 (myeloid cell leukemia sequence 1), a highly expressed antiapoptotic gene residing within the chr 3 amplicon peak. CGH on mouse cDNA microarrays therefore represents a reliable method for the high-resolution characterization of CNAs in murine tumors, and a powerful approach for elucidating the molecular events in tumor development and progression in murine models. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Using regression correlation
Project description:We conducted microarray-based comparative genomic hybridization (array-CGH) with a DNA chip carrying 2,464 BAC clones to examine genomic aberrations of 236 neuroblastomas (112 sporadic and 124 mass screening-detected). In paralell, gene-expression profiling was also performed by using in-house cDNA microarrays. Keywords: Comparative genomic hybridization
Project description:Reuse of materials in DNA hybridization based methods has been known since the advent of Southern membranes. Array based comparative genomic hybridization is essentially Southern hybridization with multiple probes immobilized on a solid surface. We have shown that comparative genomic hybridization microarrays fabricated with maskless array synthesizer technology can be used up to four times with application of 1,3-dimethylurea as array-stripping agent. We reproducibly detected chromosomal aberrations, 0.6 to 22.4 Mb in size, in four hybridization rounds using regenerated microarray slides. We have also demonstrated that regenerated arrays can detect smaller alterations, 16 – 200 kbp, such as common copy number variants, as well as complex aberration profiles in tumor.
Project description:This set includes individuals from 10 different primate species whose genomic DNA was used in an array-based comparative genomic hybridization (aCGH)using human cDNA microarrays to detect gene copy number variation across 10 primate species. An organism part comparison experiment design type compares tissues, regions, organs within or between organisms. Keywords: organism_part_comparison_design, array CGH
Project description:Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the cancer process. Here, we engineered lymphoma-prone mice with chromosomal instability to assess the utility of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Integrating with targeted re-sequencing, our comparative oncogenomic studies efficiently identified FBXW7 and PTEN as commonly deleted or mutated tumor suppressors in human T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). More generally, the murine cancers acquire widespread recurrent clonal amplifications and deletions targeting loci syntenic to alterations present in not only human T-ALL but also diverse tumors of hematopoietic, mesenchymal and epithelial types. These results thus support the view that murine and human tumors experience common biological processes driven by orthologous genetic events as they evolve towards a malignant phenotype. The highly concordant nature of genomic events encourages the use of genome unstable murine cancer models in the discovery of biologically relevant driver events in human cancer. Keywords: comparative genomic hybridization, genetic modification