Transcriptomics,Genomics

Dataset Information

157

Global gene expression profiling reveal distinct molecular profiles between p53-sensitive and p53-resistant T-cell lymphomas


ABSTRACT: TP53 mutations occur in approximately 50% of all human tumors with increased frequency in aggressive cancers that are notoriously difficult to treat. Additionally, p53 missense mutations are remarkably predictive of refractoriness to chemo/radiotherapy in various malignancies. These observations have led to the development of mutant-p53 targeting agents that restore p53 function. An important unknown is which p53-mutant tumors will respond to p53 reactivation-based therapies. Here we found a heterogeneous impact on therapeutic response to p53 restoration, suggesting it will unlikely be effective as a single therapy. The goal of the study was to identify the pathways conferring resistance or sensitivity to genetic p53 restoration in tumors with a p53 missense mutaiton Results:We sequenced the transcriptome of tumors that were sensitive or resistant to p53 restoration and found that TNF signaling was activated in p53-sensitive tumors. Overall design: 12 independent biological samples were analyzed to compare tumors that were sensitive (n=8) or resistant (n=4) to genetic p53 restoration

INSTRUMENT(S): Illumina HiSeq 3000 (Mus musculus)

SUBMITTER: Guillermina Lozano 

PROVIDER: GSE109883 | GEO | 2018-05-01

REPOSITORIES: GEO

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Publications

Synergistic and additive effect of retinoic acid in circumventing resistance to p53 restoration.

Larsson Connie A CA   Moyer Sydney M SM   Liu Bin B   Michel Keith A KA   Pant Vinod V   Yang Peirong P   Wong Justin J   El-Naggar Adel K AK   Krahe Ralf R   Lozano Guillermina G  

Proceedings of the National Academy of Sciences of the United States of America 20180213 9


TP53 mutations occur in ∼50% of all human tumors, with increased frequency in aggressive cancers that are notoriously difficult to treat. Additionally, p53 missense mutations are remarkably predictive of refractoriness to chemo/radiotherapy in various malignancies. These observations have led to the development of mutant p53-targeting agents that restore p53 function. An important unknown is which p53-mutant tumors will respond to p53 reactivation-based therapies. Here, we found a heterogeneous  ...[more]

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