Optimal anti-EGFR Treatment of mCRC Patients with Low-Frequency RAS Mutation
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Ras-mutant Metastatic Colorectal Cancer
PROVIDER: 2538373 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:The differential expression of microRNAs in Ras transformed epithelial cells of human and rat origin was investigated. Here we describe the group of miRNAs differentially expressed in two Ras transformed cell lines and defined it as a miRNA Ras signatures. We show that expression of these miRNAs are also affected in different primary tumors with high frequency of Ras mutation. We demonstate that introduction of different miRNAs lost during Ras transformation have big influence on cellular phenotype and mRNA expression. Importance of Ras pathway dependent transcription factors for miRNA regulation was shown as well. The complexity of miRNA – signal transduction pathways interactions and importance of miRNA regulation in Ras dependent malignant tumor formation is discussed.
2020-08-28 | GSE46794 | GEO
Project description:The differential expression of microRNAs in Ras transformed epithelial cells of human and rat origin was investigated. Here we describe the group of miRNAs differentially expressed in two Ras transformed cell lines and defined it as a miRNA Ras signatures. We show that expression of these miRNAs are also affected in different primary tumors with high frequency of Ras mutation. We demonstate that introduction of different miRNAs lost during Ras transformation have big influence on cellular phenotype and mRNA expression. Importance of Ras pathway dependent transcription factors for miRNA regulation was shown as well. The complexity of miRNA – signal transduction pathways interactions and importance of miRNA regulation in Ras dependent malignant tumor formation is discussed.
2020-08-28 | GSE46301 | GEO
Project description:We have adapted a commercial assay that employs mRNA quantification based on the frequency of PCR amplicons determined by next-generation to a high-throughput semi-conductor sequencing platform (Ion-Torrent Proton). We show parallel amplification of pathway derived transcript sets/genes in 12 reference RNA samples followed by sequence-based quantification covering a dynamic range of five orders of magnitude with low technical variation.
2014-07-15 | GSE58737 | GEO
Project description:To identify the physiological effects of the multiple frequency signaling through the SIMO module of EnvZHK, we used transcriptome sequencing to study the influences of different frequency inputs to gene expressions in E.coli. From the results we found that different frequency signals through the SIMO module resulted in distinct gene expressions. Moreover, the PCA result showed a significant difference between frequency response gene expression profiles under the wildtype and the mutant EnvZHK SIMO module that the gene expression profile of the wildtype samples under middle frequencies were closer to that under high frequencies, while the gene expression profile of the mutant samples under middle frequencies were closer to that under low frequencies. Interestingly, these relationships of the expression patterns were in agreement with that of these effective frequency spectrums of the SIMO module, indicating that particular frequency signals determine the distinct gene expression profiles.
2018-07-19 | GSE117326 | GEO
Project description:CD8+ T cells that bind different regions of proteins derived from a virus are often present at different frequencies. It is thought that those virus-specific CD8+ T cells that are present at the highest frequency are predominantly responsible for control of viral infections. While the number of virus-specific CD8+ T cells is undoubtedly important, the functionality of these cells may also play a role in their anti-viral capacity. It was not known if virus-specific CD8+ T cells present at high frequencies are more functionally effective against viral infection than those present at low frequencies. In this study, we characterized the functional differences between the SIV-specific cells present at high frequencies to those present at low frequencies in the blood of rhesus monkeys infected with simian immunodeficiency virus (SIV). We found that the high-and low-frequency SIV-specific cells had different functional capacities both during acute and chronic SIV infection. We also found that the strength with which a cell interacts with the proteins derived from the virus may contribute to the functional differences between the high- and low-frequency cells. These findings further our understanding of anti-viral responses and may inform HIV vaccine design.
2014-04-24 | GSE54001 | GEO
Project description:BACKGROUND. Poorly-differentiated (PDTC) and anaplastic (ATC) thyroid cancers are rare and frequently lethal tumors, which so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next generation sequencing of 341 cancer genes in 117 PDTCs and ATCs, and a transcriptomic analysis of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas (TCGA) study of papillary thyroid cancers (PTC). RESULTS. ATCs have a greater mutation burden than PDTCs, and higher mutation frequency of TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits and histone methyltransferases. BRAF and RAS are the predominant drivers, and dictate remarkably distinct tropism for nodal vs. distant metastases in PDTC. RAS and BRAF sharply distinguish between PDTCs defined by the Turin (PDTC-Turin) vs. MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, are markedly enriched in PDTCs and ATCs, and have a striking pattern of co-occurrence with RAS. TERT promoter mutations are rare and subclonal in PTCs, whereas they are clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) shows a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs are BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared to PDTC underscore their greater virulence and higher mortality. 37 tumor specimens, including 17 poorly-differentiated and 20 anaplastic thyroid cancers were expression-profiled with Affymetrix U133 plus 2.0 array
2016-02-15 | E-GEOD-76039 | biostudies-arrayexpress
Project description:We have adapted a commercial assay that employs mRNA quantification based on the frequency of PCR amplicons determined by next-generation to a high-throughput semi-conductor sequencing platform (Ion-Torrent Proton). We show parallel amplification of pathway derived transcript sets/genes in 12 reference RNA samples followed by sequence-based quantification covering a dynamic range of five orders of magnitude with low technical M-BM- variation. Expression of selected genes were profiled at four time points (0d, 10d, 20d, and 60d) during differentiation of induced pluripotent stem cells into cardiomyocytes, with three independent biological replicates at each time point.
2014-07-15 | E-GEOD-58737 | biostudies-arrayexpress
Project description:Diet may be modified seasonally or by biogeographic, demographic or cultural shifts. It can differentially influence mitochondrial bioenergetics, retrograde signalling to the nuclear genome, and anterograde signalling to mitochondria. All these interactions have the potential to influence the frequencies of mtDNA types in nature and human health. In a model laboratory system, we fed four diets varying in Protein: Carbohydrate (P:C) ratio (1:2, 1:4, 1:8 and 1:16 P:C) to four Drosophila mitotypes and assayed their frequency in population cages. The nuclear genome was standardised. When fed a high protein 1:2 P:C diet, the frequency of flies harbouring Alstonville mtDNA increased. In contrast, when fed the high carbohydrate 1:16 P:C food the incidence of flies harbouring Dahomey mtDNA increased. This result was repeated when the laboratory diet was replaced by natural fruits having high and low P:C ratios and when the nuclear genome was permuted. Quaternary structural modelling, in vitro assays of electron transport chain protein complexes, and protein gels suggested a V161L mutation in the ND4 subunit of Complex I of Dahomey mtDNA was functionally deleterious and resulted in an increase in larval development time on the 1:2 P:C diet. Conversely, the 1:16 P:C diet resulted in an elegant remodelling of energy metabolism and relative reduction in development time of larvae harbouring Dahomey mtDNA. These data question the use of mtDNA as an assumed neutral maker. We posit that humans with specific mtDNA variations may differentially metabolise carbohydrates, which has implications for a variety of first-world diseases including cardiovascular disease, diabetes, obesity and perhaps Parkinson’s Disease.
2018-11-07 | MTBLS724 | MetaboLights
Project description:BACKGROUND. Poorly-differentiated (PDTC) and anaplastic (ATC) thyroid cancers are rare and frequently lethal tumors, which so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next generation sequencing of 341 cancer genes in 117 PDTCs and ATCs, and a transcriptomic analysis of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas (TCGA) study of papillary thyroid cancers (PTC). RESULTS. ATCs have a greater mutation burden than PDTCs, and higher mutation frequency of TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits and histone methyltransferases. BRAF and RAS are the predominant drivers, and dictate remarkably distinct tropism for nodal vs. distant metastases in PDTC. RAS and BRAF sharply distinguish between PDTCs defined by the Turin (PDTC-Turin) vs. MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, are markedly enriched in PDTCs and ATCs, and have a striking pattern of co-occurrence with RAS. TERT promoter mutations are rare and subclonal in PTCs, whereas they are clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) shows a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs are BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared to PDTC underscore their greater virulence and higher mortality.
2016-02-15 | GSE76039 | GEO
Project description:CD8+ T cells that bind different regions of proteins derived from a virus are often present at different frequencies. It is thought that those virus-specific CD8+ T cells that are present at the highest frequency are predominantly responsible for control of viral infections. While the number of virus-specific CD8+ T cells is undoubtedly important, the functionality of these cells may also play a role in their anti-viral capacity. It was not known if virus-specific CD8+ T cells present at high frequencies are more functionally effective against viral infection than those present at low frequencies. In this study, we characterized the functional differences between the SIV-specific cells present at high frequencies to those present at low frequencies in the blood of rhesus monkeys infected with simian immunodeficiency virus (SIV). We found that the high-and low-frequency SIV-specific cells had different functional capacities both during acute and chronic SIV infection. We also found that the strength with which a cell interacts with the proteins derived from the virus may contribute to the functional differences between the high- and low-frequency cells. These findings further our understanding of anti-viral responses and may inform HIV vaccine design. Peripheral blood was collected on days 14, 21, 28, 35, 42, 56, 70, and and 210 after inoculation with SIVmac251. Plasma viral RNA from these samples was measured using an ultra-sensitive branched DNA amplification assay (Siemens Diagnostics, Berkeley, CA). PBMC were stained with p11C and p54AS tetramers and CD3 and CD8 antibodies at 4°C. Tetramer-positive single CD3+CD8+ lymphocytes were sorted to greather than 95% purity into RNAprotect (Qiagen) at 4°C. RNA was isolated using a Trizol (Invitrogen) extraction protocol. Briefly, 0.8 ml of Trizol were added to the cell pellet and incubated for 5 minutes at room temperature and 0.16 ml of chloroform were added, shaken vigorously by hand for 15 seconds, incubated at room temperature for 2-3 minutes and centrifuged at 13,000 rpm for 15 minutes at 4ºC. The colorless upper aqueous phase was carefully collected and transferred to a new tube containing 2 ?l of linear acrylamide for mixing. An equal volume of isopropyl alcohol was then added and mixed. The mixture was incubated at room temperature for 10 minutes and centrifuged at 13,000 rpm for 10 minutes at 4ºC. The supernatant was collected and the RNA was washed with 1 ml of 70% ethanol and centrifuged at 10,500 rpm for 5 minutes at 4ºC. The supernatant was completely removed and the RNA pellet was allowed to air-dry. The RNA was then resuspended in RNase-free water and stored at -80ºC. RNA integrity was tested using an Agilent Bioanalyzer. RNA was then amplified using the TargetAmp 2-Round Biotin-aRNA Amplification Kit 3.0 (Epicentre Biotechnologies) according the manufacturer’s instructions. Amplified biotinylated antisense-RNA (aRNA) was resuspended in RNase-free water and stored at -80ºC. Nanodrop ND-1000 was used to determine the biotinylatedaRNA concentration and an Agilent Bioanalyzer was used to determine its integrity.Amplified aRNA was hybridized to Illumina Human HT-12 Expression BeadChips according to the manufacturer instructions and was stained with Streptavidin Cy3 for detection (Illumina, San Diego, CA, USA).
2014-04-24 | E-GEOD-54001 | biostudies-arrayexpress