Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA642016 | ENA |
REPOSITORIES: ENA
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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:Unique microRNA profiles in EGFR-mutated lung adenocarcinomas
| PRJNA209985 | ENA
Project description:The success of targeted therapies creates a need to discriminate tumors accurately by their histological and genetic characteristics. Here, we used cDNA microarray analysis to identify gene expression profiles and single markers that recapitulate the pathological and genetic background (i.e., BRAF, EGFR, KRAS, LKB1, PIK3CA, and TP53 gene alterations) of non-small cell lung cancer (NSCLC). Gene expression profiles were determined for 6 normal lung tissues and 69 lung tumors from patients diagnosed with NSCLC. We performed an unsupervised hierarchical clustering with the most variably expressed transcript to investigate whether there was evidence for natural grouping samples based on similarity in gene expression profiles. We examined the relationship between the clusters of tumors and patient and tumor characteristics such as gender, smoking status, histological type, degree of differentiation, tumor size, lymph node involvement and genetic background. We used a supervised analysis to identify the genes that are important for distinguishing subgroups of tumors defined by histological type. Moreover, we used this supervised approach to search for markers that characterize those tumors carrying EGFR, KRAS, PIK3CA and TP53 alterations. We identify several genes with characteristic patterns of expression in each tumor histological type (adenocarcinoma and squamous cell carcinoma) and we found that the presence of EGFR mutations result in a particular expression profile. Keywords: Transciption profiling of tumors with different histological and genetic background. We analyzed 69 NSCLC tumors. All the samples were characterized by histological type and by the presence of alterations at genes that are known to be involved in lung carcinogenesis. Mutational analysis of BRAF, EGFR, KRAS, and LKB1 is provided only for adenocarcinomas and analysis of alterations at PIK3CA gene (mutational analysis or gene amplification by FISH analysis) is provided only for 47 of the tumors. We analyzed gene expression profiles to identify those genes that are differentially expressed between two subgroups by t-test: 1) adenocarcinomas vs. squamous cell carcinomas; 2) tumors with mutation at EGFR gene vs. wild type tumors; 3) tumors with mutation at KRAS gene vs. wild type tumors; 4) tumors with mutation at TP53 gene vs. wild type tumors; 5) tumors with alterations (mutation or gene amplification) at PIK3CA gene vs. wild type tumors.
2008-07-22 | E-GEOD-8569 | biostudies-arrayexpress
Project description:We performed RNA-seq using 19 human surgically-resected lung adenocarcinomas to investigate of difference between EGFR-mutated and wild-type lung adenocarcinomas.
2020-02-25 | GSE141569 | GEO
Project description:In lung and prostate adenocarcinomas, neuroendocrine (NE) transformation to an aggressive derivative resembling small cell lung cancer (SCLC) is associated with poor prognosis. We previously described dependency of SCLC on the nuclear transporter exportin 1. Here we explored the role of exportin 1 in NE transformation. We observed upregulated exportin 1 in lung and prostate pre-transformation adenocarcinomas. Exportin 1 was induced upregulated following genetic inactivation of TP53 and RB1 in lung and prostate adenocarcinoma cell lines, accompanied by increased sensitivity to the exportin 1 inhibitor selinexor in vitro. Exportin 1 inhibition prevented NE transformation and extended response to targeted therapies in both lung anddifferent TP53/RB1-inactivated prostate adenocarcinoma xenograft models that acquire NE features upon treatment with the AR inhibitor enzalutamide, and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-derived xenograft (PDX) model exhibiting combined adenocarcinoma/SCLC histology. Ectopic SOX2 expression restored the enzalutamide-promoted NE transformationNE phenotype on adenocarcinoma-to-NE transformation xenograft models despite selinexor treatment. Selinexor sensitized NE-transformed lung and prostate small cell carcinoma PDXs tumors after NE transformation to standard cytotoxics. Together these data nominate exportin 1 inhibition as a novel potential therapeutic approach target to constrain lineage plasticity and prevent or treat NE transformation in lung and prostate adenocarcinoma.
2023-07-12 | GSE237071 | GEO
Project description:Background: Although TP53 gain-of-function (GOF) mutations promote cancer survival, its effect on EGFR-TKI efficacy remains unclear. We established EGFR-mutant lung cancer cell lines expressing various TP53 genotypes using CRISPR-Cas9 technology and found that TP53-GOF mutant cells develop an early resistance to EGFR-TKI osimertinib.The goal of this study is to elucidate the mechanisms underlying resistance to osimertinib treatment in TP53 GOF mutations through comprehensive gene analysis using ChIP-seq.
2024-01-22 | GSE253478 | GEO
Project description:Selective Loss of RB in Resistant EGFR Mutant Lung Adenocarcinomas that Transform to SCLC [CGH]
| PRJNA271817 | ENA
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Selective Loss of RB in Resistant EGFR Mutant Lung Adenocarcinomas that Transform to SCLC [gene expression]
| PRJNA270744 | ENA
Project description:Cancer genome sequencing has uncovered substantial complexity in the mutational landscape of tumors. Given this complexity, experimental approaches are necessary to establish the impact of combinations of genetic alterations on tumor biology and to uncover genotype-dependent effects on drug sensitivity. In lung adenocarcinoma, EGFR mutations co-occur with many putative tumor suppressor gene alterations, however the extent to which these alterations contribute to tumor growth and their response to therapy in vivo has not been explored experimentally. By integrating a novel mouse model of oncogenic EGFR-driven Trp53-deficient lung adenocarcinoma with multiplexed CRISPR–Cas9-mediated genome editing and tumor barcode sequencing, we quantified the effects of inactivation of ten putative tumor suppressor genes. Inactivation of Apc, Rb1, or Rbm10 most strongly promoted tumor growth. Unexpectedly, inactivation of Lkb1 or Setd2 – which were the strongest drivers of tumor growth in an oncogenic Kras-driven model – reduced EGFR-driven tumors growth. These results were consistent with the relative frequency of these tumor suppressor gene alterations in human EGFR and KRAS-driven lung adenocarcinomas. Furthermore, Keap1 inactivation reduced the sensitivity of tumors to osimertinib in the EGFRL858R;p53flox/flox model. Importantly, in human EGFR/TP53 mutant lung adenocarcinomas, mutations in the KEAP1 pathway correlated with decreased time on tyrosine kinase inhibitor treatment. Our study highlights how genetic alterations can have dramatically different biological consequences depending on the oncogenic context and that the fitness landscape can shift upon drug treatment.
2021-02-01 | GSE146550 | GEO