Genomics

Dataset Information

16

Atm-/-,mTerc-/-,p53-/- triple knock-out lymphoma vs normal mouse DNA (GPL4092)


ABSTRACT: 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 Overall design: 13 lymphoma samples from Atm-/-, mTerc-/-, p53-/- triple knock-out mice were analyzed. DNA from matched mouse of the same tumorsample was used as reference. Each sample was hybridized with dye-swap replica. 44K of 244K probes were extracted for analysis in order to combine these 13 samples with other 22 samples which are hybridized on Agilent's 44K mouse CGH arrays, GPL2884

INSTRUMENT(S): Agilent-014695 Mouse Genome CGH Microarray 244A (G4415A) (Feature Number version)

SUBMITTER: bin feng  

PROVIDER: GSE7597 | GEO | 2007-06-05

SECONDARY ACCESSION(S): PRJNA105521

REPOSITORIES: GEO

altmetric image

Publications

Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers.

Maser Richard S RS   Choudhury Bhudipa B   Campbell Peter J PJ   Feng Bin B   Wong Kwok-Kin KK   Protopopov Alexei A   O'Neil Jennifer J   Gutierrez Alejandro A   Ivanova Elena E   Perna Ilana I   Lin Eric E   Mani Vidya V   Jiang Shan S   McNamara Kate K   Zaghlul Sara S   Edkins Sarah S   Stevens Claire C   Brennan Cameron C   Martin Eric S ES   Wiedemeyer Ruprecht R   Kabbarah Omar O   Nogueira Cristina C   Histen Gavin G   Aster Jon J   Mansour Marc M   Duke Veronique V   Foroni Letizia L   Fielding Adele K AK   Goldstone Anthony H AH   Rowe Jacob M JM   Wang Yaoqi A YA   Look A Thomas AT   Stratton Michael R MR   Chin Lynda L   Futreal P Andrew PA   DePinho Ronald A RA  

Nature 20070521 7147


Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly delete  ...[more]

Similar Datasets

2007-06-05 | GSE7599 | GEO
2007-06-05 | GSE7602 | GEO
2007-06-05 | GSE7603 | GEO
2007-06-05 | GSE7606 | GEO
2007-06-05 | GSE7600 | GEO
2007-06-05 | GSE7607 | GEO
2014-05-02 | E-GEOD-7602 | ArrayExpress
2014-05-02 | E-GEOD-7599 | ArrayExpress
2014-05-02 | E-GEOD-7604 | ArrayExpress
2014-05-02 | E-GEOD-7606 | ArrayExpress