Transcriptomics

Dataset Information

5

Yap1/Birc, c-Met and N-ras DNA amplifications are mutually exclusive in mouse mammary tumors.


ABSTRACT: Tumors acquire somatic DNA copy number aberrations, leading to activation of oncogenes and inactivation of tumor suppressors. Many studies have focused on the analysis of single copy number aberrations and associated driver genes, but few studies have performed combinatorial analyses. We propose a genome-wide scoring framework to find mutually exclusive gains and losses. Mutually exclusive copy number aberrations can identify genes whose oncogenic function is redundant, either by functioning in the same pathway or in a parallel pathway. As one gene is aberrated the selective pressure for its partner is alleviated which leads to a mutually exclusive perturbation pattern. In a dataset of mouse models for invasive lobular carcinoma we found three mutually exclusive DNA amplifications, containing several well-known oncogenes: the Met proto-oncogene on chromosome 6, the cluster of Birc2, Birc3 and Yap1 genes on chromosome 9, and Nras on chromosome 3. Furthermore, gene expression or protein expression of these genes correlates very well with copy number data indicating that they are the target of the amplification. Although homologous amplifications in human tumors are rare, the mutual exclusivity of MET, BIRC/YAP1 and NRAS is maintained in a variety of cancer types. This suggests a novel function for YAP1 in the mitogen-activated signaling pathway by association with MET and NRAS, known players in this pathway. This function is independent to the propensity of YAP1 to cause Epithelial-to-Mesenchymal transition. aCGH data of 67 mouse mammary tumors from K14-Cre and WAP-Cre driven P53-F/F;Cdh1-F/F animals - tumor DNA hybridized against same-animal splenic DNA

ORGANISM(S): Mus musculus  

SUBMITTER: Sjoerd Klarenbeek   Christiaan Klijn  Tanya M Braumuller  Lodewyk F Wessels  Jos Jonkers  Marcel J Reinders  Christiaan Nicolaas Klijn  Jan Bot 

PROVIDER: E-GEOD-28432 | ArrayExpress | 2011-12-01

SECONDARY ACCESSION(S): GSE28432PRJNA139235

REPOSITORIES: GEO, ArrayExpress

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