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MYC drives resistance to PI3K/mTOR targeted inhibition (Sty SNP array)

ABSTRACT: Genomic copy-number changes were measured using 250K StyI SNP arrays after selection of cells to enrich for resistance to BEZ235. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted using Qiagen DNeasy from engineered human cell-lines. Resulting alterations in copy numbers were calculated based on SNP intensities.

ORGANISM(S): Homo sapiens

SUBMITTER: Nina Ilic

PROVIDER: E-GEOD-25170 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis.

Ilic Nina N Utermark Tamara T Widlund Hans R HR Roberts Thomas M TM

Proceedings of the National Academy of Sciences of the United States of America 20110829 37

The PI3K pathway is frequently activated in cancer; therefore, considerable effort is focused on identifying compounds that can inhibit specific pathway components, particularly the hallmark oncogene PIK3CA. Although targeted inhibition of a cancer survival gene holds significant promise, there are concerns that drug resistance may emerge within the cancerous cells, thus limiting clinical efficacy. Using genetically defined human mammary epithelial cells, we evolved resistance to the PI3K/mammal ...[more]

PMID: 21876152

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MYC drives resistance to PI3K/mTOR targeted inhibition (Sty SNP array)

Project description:Genomic copy-number changes were measured using 250K StyI SNP arrays after selection of cells to enrich for resistance to BEZ235. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted using Qiagen DNeasy from engineered human cell-lines.

2011-08-31 | GSE25170 | GEO

PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis

Project description:This SuperSeries is composed of the following subset Series: GSE25170: MYC drives resistance to PI3K/mTOR targeted inhibition (Sty SNP array) GSE25172: MYC drives resistance to PI3K/mTOR targeted inhibition (gene expression) Refer to individual Series

2011-09-13 | E-GEOD-25173 | biostudies-arrayexpress

MYC drives resistance to PI3K/mTOR targeted inhibition (gene expression)

Project description:Gene expression signatures were measured after treatment of cells with 50nM BEZ235. Affymetrix HG-U133AV2 expression arrays were performed according to the manufacturer's directions using RNA extracted by Qiagen RNeasy from engineered human cell-lines grown for 72h in the presence of 50nM BEZ235 Resulting expression signatures where derived based on phenotypic properties(resistance to BEZ235) of the cells (enriched vs GFP/HR).

2011-08-30 | E-GEOD-25172 | biostudies-arrayexpress

Amplification in alveolar rhabdomyosarcoma

Project description:Genomic and clinical analyses of major amplification events in alveolar rhabdomyosarcoma Affymetrix SNP 50K XbaI chips were used to anaylyze 57 alveolar rhabdomyosarcoma samples and selected cases were further analyzed using Affymetrix SNP 250K StyI chips

2010-10-16 | E-GEOD-24715 | biostudies-arrayexpress

Gastrointestinal Adenocarcinomas of the Esophagus, Stomach, and Colon Exhibit Distinct Patterns of Genome Instability and Oncogenesis.

Project description:This SuperSeries is composed of the following subset Series: GSE36458: Affymetrix SNP 6.0 array data for colon, gastric and esophageal adenocarcinoma cancer types GSE36459: Affymetrix 250K StyI SNP array data for gastric and esophageal adenocarcinoma cancer types Refer to individual Series

2012-08-31 | E-GEOD-36460 | biostudies-arrayexpress

MS-based quantitative proteomic analysis of ribosomal fractions from wild-type and Zeb1-overexpressing human mammary epithelial cell

Project description:Epithelial-mesenchymal transition (EMT) involves profound changes in cell morphology, driven by transcriptional and epigenetic reprogramming. However, it emerges that translation and the ribosome composition play also key role in establishing physio-pathological phenotypes. Using genome-wide analyses, we report significant rearrangement of the translational landscape and machinery during EMT. Specifically, a mesenchymal cell line overexpressing the EMT transcription factor ZEB1 shows alterations in translational reprogramming and fidelity. Considering the change in translational activity of ZEB1-overexpressing mesenchymal cells, including in fidelity activity, we sought for changes in ribosome composition. We thus performed a riboproteome approach, i.e., mass spectrometry (MS)-based quantitative proteomic analysis of purified cytoplasmic ribosomes to highlight any change in relative amount of individual ribosomal proteins between wild-type and ZEB1-overexpressing human mammary epithelial cells.

2024-11-02 | PXD047409 | Pride

MSNP data for normal blood, normal bone marrow, CD34+ cells and placenta samples

Project description:A novel method for detecting genome-wide ASM (allele-specific methylation) was developed by modification of the Affymetrix 250K StyI SNP arrays. Using this method, and the above mentioned samples, we consistently detected ASM in non-imprinted regions of the genome. Interestingly, ASM appears to be strongly correlated with the SNP sequences in cis. DNA from various sources (6 normal blood, 2 normal bone marrow, 2 CD34+ bone marrow, and 3 placenta samples) was genotyped and ASM was scored as an allele call conversion from 'AB' (heterozygous) to 'AA' or 'BB' (homozygous) in the StyI+HpaII genomic representation, compared to the StyI-only representation. Each sample was subjected to 5 runs of genotyping on the 250K StyI array, including 2 StyI alone, 2 StyI+HpaII and 1 StyI+MspI.

2008-05-10 | E-GEOD-11409 | biostudies-arrayexpress

SNP array genomic profiling of PTCL NOS

Project description:DNA extracted from frozen tissue of 47 peripheral T-cell lymphomas–not otherwise specified [PTCL-NOS] was hybridized to 250k StyI SNP arrays

2010-03-17 | GSE15842 | GEO

Targeting PI3K/mTOR signaling exerts potent antitumor activity in pheochromocytoma in vivo

Project description:Pheochromocytomas (PCC) are mostly benign tumors, amenable to complete surgical resection. However, 10–17% of cases can become malignant, and once metastasized, there is no curative treatment for this disease. Given the need to identify effective therapeutic approaches for PCC, we evaluated the antitumor potential of the dual PI3K/mTOR inhibitor BEZ235 against these tumors. We employed an in vivo model of endogenous PCCs (MENX mutant rats), which closely recapitulate the human tumors. Mutant rats with PCCs were treated with 2 doses of BEZ235 (20 and 30 mg/kg), or with placebo, for 2 weeks. Treatment with BEZ235 induced cytostatic and cytotoxic effects on rat PCCs, which could be appreciated by both staining the tumors ex vivo with appropriate markers, and non-invasively by functional imaging (diffusion weighted-DW-MRI) in vivo. Transcriptomic analyses of tumors from rats treated with BEZ235 or placebo identified potential mediators of therapy response. Slc6a2, encoding the norepinephrine transporter (NET), was downregulated in a dose-dependent manner by BEZ235 in rat PCCs. Moreover, BEZ235 reduced Slc6a2/NET expression also in PCC cell lines (PC12, MPC, MTT). Studies of a BEZ235-resistant derivative of the MPC cell line (MPCR) confirmed that the reduction of NET expression associates with the response to the drug. Reduction of NET expression following BEZ235 treatment in vivo could be monitored by Positron Emission Tomography (PET) using a tracer targeting NET. Altogether, we demonstrate the efficacy of BEZ235 against PCC in vivo, and show that functional imaging can be employed to monitor the response of PCC to PI3K/mTOR inhibition therapy.

2016-11-03 | GSE83401 | GEO

MYC drives resistance to PI3K/mTOR targeted inhibition (gene expression)

2011-08-31 | GSE25172 | GEO