Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA315971 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The goal of this study was to determine genes affected by expressing KRAS mutation (G12V) in NCI-H1703 cells This data was used in Meng Wang et. al. Cancer Research 2016 to determine the alterations of gene expression profiling associated with expression of KRAS mutation (G12V). The experiment uses a pBABE-Puro vector encoding KRAS G12V and a corresponding empty vector control.
2016-03-23 | E-GEOD-79486 | biostudies-arrayexpress
Project description:The goal of this study was to determine genes affected by expressing KRAS mutation (G12V) in NCI-H1703 cells This data was used in Meng Wang et. al. Cancer Research 2016 to determine the alterations of gene expression profiling associated with expression of KRAS mutation (G12V).
2016-03-23 | GSE79486 | GEO
Project description:Purpose: The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. The development of new and effective treatment has been and continues to be a major public health imperative. Methods: We report mutational and copy number analysis of 44 predominantly early-staged gallbladder tumors and 5-gallbladder cancer cell lines by a combination of directed and whole exome sequencing at an average coverage of 100X and above. Using gallbladder cancer cell lines and xenograft mouse models we performed phospho-proteome array profiling, followed by an in-depth functional characterization. Results: We describe recurrent activating ERBB2 somatic mutation in 6 of 44 gallbladder primary tumors with an overall mutation frequency of 13%, along with KRAS activating mutations in 3 of 44 samples. Consistent with whole exome findings, a phospho-proteomic array profile of 49-tyrosine kinase revealed constitutive phosphorylation of ERBB2 and EGFR that were found to heterodimerize. We demonstrate that treatment with ERBB2-specific, EGFR-specific shRNA or with covalent EGFR family inhibitor BIBW-2992 inhibits transformation, survival, migration, invasion, and tumor forming characteristics of gallbladder cancer cells harboring wild type or KRAS (G13D) but not KRAS (G12V) mutation. Furthermore, we show in vivo reduction in tumor size is paralleled by a reduction in the amounts of phospho-ERK in KRAS (G13D) but not in KRAS (G12V) xenografts, validating the in vitro findings Conclusion: Findings from this study implicate ERBB2 as an important therapeutic target in early stage gallbladder cancer. We also present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.
2018-12-29 | E-MTAB-6619 | biostudies-arrayexpress
Project description:To explore the distinct mechanism of KRAS G12V and G12D mutation. We used microarray to explore the distinct differences in gene expression profiles of H838 KRAS mutation isogenic cell lines
2020-05-21 | GSE119146 | GEO
Project description:Oncogenic KRAS mutations are prevalent in colorectal cancer (CRC) and are associated with poor prognosis and resistance to therapy. There is a substantial diversity of KRAS mutant alleles observed in CRC. Emerging clinical and experimental analysis of common KRAS mutations suggest that each mutation differently influences the clinical properties of a disease and response to therapy. Although there is some evidence to suggest biological differences between mutant KRAS alleles, these are yet to be fully elucidated. One approach to study allelic variation involves the use of isogenic cell lines that express different endogenous Kras mutants. Here, we generated Kras isogenic Apc-/- mouse colon epithelial cell lines using CRISPR-driven genome editing by altering the original G12D Kras allele to G12V, G12R, or G13D. We utilized these cell lines to perform transcriptomic and proteomic analysis to compare different signaling properties between these mutants. Both screens indicate significant differences in pathways relating to cholesterol and lipid regulation that we validated with targeted metabolomic measurements and isotope tracing. We found that these processes are upregulated in G12V lines through increased expression of nuclear SREBP1 and higher activation of mTORC1. G12V cells showed higher expression of ACSS2 and ACSS2 inhibition sensitized G12V cells to MEK inhibition. Finally, we found that ACSS2 plays a crucial role early in the development of G12V mutant tumors, in contrast to G12D mutant tumors. These observations highlight differences between KRAS mutant cell lines in their signaling properties. Further exploration of these pathways may prove to be valuable for understanding how specific KRAS mutants function, and identification of novel therapeutic opportunities in CRC.
2025-05-02 | PXD050157 | Pride
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net ) : 165 lung adenocarcinomas without prior chemotherapy, hybridized on Illumina SNP HumanCNV370 and Affymetrix HGU133Plus2 arrays. Project leader : Prof. Pierre FOURET (pierre.fouret@igr.fr). Note: Bronchiolo-alveolarComponent : a non invasive tumor component shown in well differentiated tumor cells. EGFR Gene Mutation Status: Gene mutation status of epidermal growth factor receptor (erythroblastic leukemia viral (v; -erb-b) ; oncogene homolog, avian) ; HGNC:3236 ; Approved Symbol:EGFR; Chromosome:7p12 ; UniProt ; ID:P00533 ; OMIMID:131550 ; EntrezGeneID:1956 ; ; RefSeq:NM_201283 ; M=mutated ; WT=non mutated=wild type. KRAS Gene Mutation Status: Gene mutation status of v-Ki-ras2 Kirsten rat ; sarcoma viral oncogene homolog ; HGNC:6407 ; Approved Symbol:KRAS ; Chromosome:12p12.1 ; UniProtID:P01116; OMIM ID:190070 ; EntrezGeneID:3845 ; ;RefSeq:NM_033360 ; M=yes=mutated ; WT=non mutated.
2012-10-19 | E-MTAB-923 | biostudies-arrayexpress
Project description:Despite KRAS-G12V being the second most common KRAS mutation in cancer, there are no approved direct KRAS-G12V inhibitors. Difficulties with inhibiting oncogenes using conventional approaches have prompted the use of RNAi as a therapeutic approach. RNAi has faced numerous obstacles as a cancer therapeutic, including the lack of cancer-specific tissue targeting, rapid oligonucleotide nuclease degradation and clearance from the circulation. Recently, the use of targetable ligands conjugated to chemically modified siRNAs has shown remarkable promise in circumventing these barriers. We demonstrate that EFTX-G12V is highly selective for KRAS-G12V and has improved therapeutic activity over pan-KRAS targeting, including enhanced inhibition of several cancer hallmarks. With a novel RNAi delivery platform, we demonstrate tumor silencing of KRAS-G12V and significant anti-tumor activity across several cancer models. Our findings represent a technologic advance in oncogene targeting using RNAi and reveal new biologic insights in KRAS targeting that may have broad implications with regards to safety and efficacy. This dataset collects the RNA-Seq data for the SKCO1 cell line.
2025-07-16 | GSE278020 | GEO
Project description:Despite KRAS-G12V being the second most common KRAS mutation in cancer, there are no approved direct KRAS-G12V inhibitors. Difficulties with inhibiting oncogenes using conventional approaches have prompted the use of RNAi as a therapeutic approach. RNAi has faced numerous obstacles as a cancer therapeutic, including the lack of cancer-specific tissue targeting, rapid oligonucleotide nuclease degradation and clearance from the circulation. Recently, the use of targetable ligands conjugated to chemically modified siRNAs has shown remarkable promise in circumventing these barriers. We demonstrate that EFTX-G12V is highly selective for KRAS-G12V and has improved therapeutic activity over pan-KRAS targeting, including enhanced inhibition of several cancer hallmarks. With a novel RNAi delivery platform, we demonstrate tumor silencing of KRAS-G12V and significant anti-tumor activity across several cancer models. Our findings represent a technologic advance in oncogene targeting using RNAi and reveal new biologic insights in KRAS targeting that may have broad implications with regards to safety and efficacy. This dataset collects the RNA-Seq data for the H727 cell line.
2025-07-16 | GSE278019 | GEO
Project description:Despite KRAS-G12V being the second most common KRAS mutation in cancer, there are no approved direct KRAS-G12V inhibitors. Difficulties with inhibiting oncogenes using conventional approaches have prompted the use of RNAi as a therapeutic approach. RNAi has faced numerous obstacles as a cancer therapeutic, including the lack of cancer-specific tissue targeting, rapid oligonucleotide nuclease degradation and clearance from the circulation. Recently, the use of targetable ligands conjugated to chemically modified siRNAs has shown remarkable promise in circumventing these barriers. We demonstrate that EFTX-G12V is highly selective for KRAS-G12V and has improved therapeutic activity over pan-KRAS targeting, including enhanced inhibition of several cancer hallmarks. With a novel RNAi delivery platform, we demonstrate tumor silencing of KRAS-G12V and significant anti-tumor activity across several cancer models. Our findings represent a technologic advance in oncogene targeting using RNAi and reveal new biologic insights in KRAS targeting that may have broad implications with regards to safety and efficacy. This dataset collects the RNA-Seq data for the H441 cell line.
2025-07-16 | GSE278018 | GEO
Project description:Oncogenic KRAS mutations are prevalent in colorectal cancer (CRC) and are associated with poor prognosis and resistance to therapy. There is a substantial diversity of KRAS mutant alleles observed in CRC. Emerging clinical and experimental analysis of common KRAS mutations suggest that each mutation differently influences the clinical properties of a disease and response to therapy. Although there is some evidence to suggest biological differences between mutant KRAS alleles, these are yet to be fully elucidated. One approach to study allelic variation involves the use of isogenic cell lines that express different endogenous Kras mutants. Here, we generated Kras isogenic Apc-/- mouse colon epithelial cell lines using CRISPR-driven genome editing by altering the original G12D Kras allele to G12V, G12R, or G13D. We utilized these cell lines to perform transcriptomic and proteomic analysis to compare different signaling properties between these mutants. Both screens indicate significant differences in pathways relating to cholesterol and lipid regulation that we validated with targeted metabolomic measurements and isotope tracing. We found that these processes are upregulated in G12V lines through increased expression of nuclear SREBP1 and higher activation of mTORC1. G12V cells showed higher expression of ACSS2 and ACSS2 inhibition sensitized G12V cells to MEK inhibition. Finally, we found that ACSS2 plays a crucial role early in the development of G12V mutant tumors, in contrast to G12D mutant tumors. These observations highlight differences between KRAS mutant cell lines in their signaling properties. Further exploration of these pathways may prove to be valuable for understanding how specific KRAS mutants function, and identification of novel therapeutic opportunities in CRC.
2025-03-18 | GSE261333 | GEO