Transcriptomics

Dataset Information

30

Comparative oncogenomics identifies breast tumors enriched in functional tumor initiating cells


ABSTRACT: The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor initiating cells (TIC) and human mammary stem cells. Through cross-species analysis, we discovered mouse mammary tumors that have similar gene expression characteristics as human claudin-low tumors and were also enriched for the human TIC signature. Such claudin-low tumors were similarly rare, but came from a number of distinct mouse models including the p53 null transplant model. Here we present a molecular characterization of fifty p53 null mammary tumors as compared to other mouse models and human breast tumor subtypes. Similar to human tumors, the murine p53 null tumors fell into multiple molecular subtypes including two basal-like, a luminal, a claudin-low, and a subtype unique to this model. The claudin-low tumors also showed high gene expression of EMT inducers, low expression of the miR-200 family, and low to absent expression of both claudin 3 and E-cadherin. These murine subtypes also contained distinct genomic DNA copy number changes some of which are similarly altered in their cognate human subtype counterpart. Finally, limiting dilution transplantation revealed that p53 null claudin-low tumors are highly enriched for TICs as compared to the more common adenocarcinomas arising in the same model, thus providing a novel preclinical mouse model to investigate the therapeutic response of TICs. 107 Agilent CGH and expression microarrays

ORGANISM(S): Mus musculus  

SUBMITTER: Jason I Herschkowitz   Charles Perou 

PROVIDER: E-GEOD-27101 | ArrayExpress | 2011-08-14

SECONDARY ACCESSION(S): GSE27101PRJNA137439

REPOSITORIES: GEO, ArrayExpress

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Publications

Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells.

Herschkowitz Jason I JI   Zhao Wei W   Zhang Mei M   Usary Jerry J   Murrow George G   Edwards David D   Knezevic Jana J   Greene Stephanie B SB   Darr David D   Troester Melissa A MA   Hilsenbeck Susan G SG   Medina Daniel D   Perou Charles M CM   Rosen Jeffrey M JM  

Proceedings of the National Academy of Sciences of the United States of America 20110601 8


The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor-initiating cells (TICs) and human mammary stem cells. Through cross-species analysis, we discovered mouse mammary tumors that have similar gene expression characteristics as human cl  ...[more]

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