8cf7827e-54fd-4fd1-9ca3-9872346e8152 - samples
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ABSTRACT:
PROVIDER: EGAD00001009412 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Here, we performed genome-wide 5-mC profiling in plasma of metastatic ALK-rearranged non-small cell lung cancer (NSCLC) patients receiving tyrosine kinase inhibitor therapy. We established a strategy to identify ALK-specific 5-mC changes from cfDNA and demonstrated the suitability of the identified markers for cancer detection, prognosis and therapy monitoring. Longitudinal plasma samples (n = 79) of 21 ALK-positive NSCLC patients and 13 healthy donors were collected alongside 15 ALK-positive tumor tissue and 10 healthy lung tissue specimens. All plasma and tissue samples were analyzed by cell-free DNA methylation immunoprecipitation sequencing to generate genome-wide 5-mC profiles. Information on genomic alterations (i.e., somatic mutations/fusions and copy number alterations) determined in matched plasma samples were available from previous studies.
| EGAS00001006573 | EGA
Project description:To identify a plasma microRNA panel that could help to distinguish ALK positive with ALK negative NSCLC patients, plasma samples of 3 ALK-positive, 3 ALK-negative NSCLC, and 3 Healthy Subjects were selected for Agilent miRNA microarray analysis to detect differences in the expression levels of circulating miRNAs (n = 2568) between the above cohorts.
2017-02-07 | GSE94536 | GEO
Project description:Three separate experiments were carried out using MeDIP-seq and cfMeDIP-seq for methylome analysis. For the first experiment, different starting amounts of HCT116 cell line DNA, sheared to mimic cell-free DNA, were analyzed using MeDIP-seq and cfMeDIP-seq. In the second experiment the limit of detection of cfMeDIP-seq was tested using varying dilutions of colorectal cancer cell line DNA (HCT116) with multiple myeloma cell line DNA (MM1.S). For both cell line DNA samples, the DNA was sheared to mimic cell-free DNA. In the final experiment, we tested the enrichment of human ctDNA using cfMeDIP-seq performed on plasma collected from patient-derived xenografts (PDXs) generated in mice from two colorectal cancer patients.
2018-04-01 | GSE79838 | GEO
Project description:Structural genomic variants leading to anaplastic lymphoma kinase (ALK) gene fusions and aberrant expression of the ALK tyrosine kinase are the hallmark of subtypes of T- and B-lineage neoplasms, namely ALK-positive anaplastic large lymphoma (ALCL) and ALK-positive large B-cell lymphoma (LBCL). The latter is a rare aggressive lymphoma, which has been initially identified as a variant of diffuse LBCL (DLBCL) with plasmablastic features. Here, we performed comparative DNA methylation profiling of human and murine ALK-positive B-cell neoplasms. Array-based DNA methylation data from ALK-positive LBCL samples of eight patients were compared to that of DLBCL (n=75), multiple myeloma (MM, n=24), ALK-positive ALCL (n=12) and normal B-cell populations (n=93). ALK-positive LBCLs share a distinct DNA methylation signature similar to that of MM, characterized by lower global DNA methylation levels compared to DLBCLs and normal B-cell populations. DNA methylation alterations in ALK-positive LBCL were predominantly located in heterochromatic and polycomb-repressed regions. The epigenetic age and relative proliferative history of ALK-positive LBCL were intermediate between MM and DLBCL. B-cell neoplasms in NPM::ALK transgenic mice showed a similar hypomethylated signature when compared to normal murine B cells. Cross-species comparison indicated conservation of chromatin states and pathways affected by hypomethylation. Together, the findings suggest that in line with their phenotypical appearance human and murine ALK-positive B-cell lymphomas share an epigenetic profile more closely resembling that of plasma cell neoplasias than that of DLBCLs.
2025-09-10 | GSE289990 | GEO
Project description:Structural genomic variants leading to anaplastic lymphoma kinase (ALK) gene fusions and aberrant expression of the ALK tyrosine kinase are the hallmark of subtypes of T- and B-lineage neoplasms, namely ALK-positive anaplastic large lymphoma (ALCL) and ALK-positive large B-cell lymphoma (LBCL). The latter is a rare aggressive lymphoma, which has been initially identified as a variant of diffuse LBCL (DLBCL) with plasmablastic features. Here, we performed comparative DNA methylation profiling of human and murine ALK-positive B-cell neoplasms. Array-based DNA methylation data from ALK-positive LBCL samples of eight patients were compared to that of DLBCL (n=75), multiple myeloma (MM, n=24), ALK-positive ALCL (n=12) and normal B-cell populations (n=93). ALK-positive LBCLs share a distinct DNA methylation signature similar to that of MM, characterized by lower global DNA methylation levels compared to DLBCLs and normal B-cell populations. DNA methylation alterations in ALK-positive LBCL were predominantly located in heterochromatic and polycomb-repressed regions. The epigenetic age and relative proliferative history of ALK-positive LBCL were intermediate between MM and DLBCL. B-cell neoplasms in NPM::ALK transgenic mice showed a similar hypomethylated signature when compared to normal murine B cells. Cross-species comparison indicated conservation of chromatin states and pathways affected by hypomethylation. Together, the findings suggest that in line with their phenotypical appearance human and murine ALK-positive B-cell lymphomas share an epigenetic profile more closely resembling that of plasma cell neoplasias than that of DLBCLs.
2025-09-10 | GSE289988 | GEO
Project description:Structural genomic variants leading to anaplastic lymphoma kinase (ALK) gene fusions and aberrant expression of the ALK tyrosine kinase are the hallmark of subtypes of T- and B-lineage neoplasms, namely ALK-positive anaplastic large lymphoma (ALCL) and ALK-positive large B-cell lymphoma (LBCL). The latter is a rare aggressive lymphoma, which has been initially identified as a variant of diffuse LBCL (DLBCL) with plasmablastic features. Here, we performed comparative DNA methylation profiling of human and murine ALK-positive B-cell neoplasms. Array-based DNA methylation data from ALK-positive LBCL samples of eight patients were compared to that of DLBCL (n=75), multiple myeloma (MM, n=24), ALK-positive ALCL (n=12) and normal B-cell populations (n=93). ALK-positive LBCLs share a distinct DNA methylation signature similar to that of MM, characterized by lower global DNA methylation levels compared to DLBCLs and normal B-cell populations. DNA methylation alterations in ALK-positive LBCL were predominantly located in heterochromatic and polycomb-repressed regions. The epigenetic age and relative proliferative history of ALK-positive LBCL were intermediate between MM and DLBCL. B-cell neoplasms in NPM::ALK transgenic mice showed a similar hypomethylated signature when compared to normal murine B cells. Cross-species comparison indicated conservation of chromatin states and pathways affected by hypomethylation. Together, the findings suggest that in line with their phenotypical appearance human and murine ALK-positive B-cell lymphomas share an epigenetic profile more closely resembling that of plasma cell neoplasias than that of DLBCLs.
2025-09-10 | GSE289985 | GEO
Project description:Using cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), we analyzed methylation profiles in 93 plasma samples from 77 pediatric brain tumor patients and 16 non-neoplastic patients. Binomial GLMnet classifiers of tumor and tumor subtypes were built in training sets, and performance was evaluated in test sets. The methylation profiles from plasma cfMeDIP-seq discriminated tumor from non-tumor patients with 0.83 accuracy (precision = 0.93, sensitivity = 0.86, and specificity = 0.67). Among major tumor subtypes vs. nontumors, circumscribed astrocytic glioma showed an accuracy of 0.86 (precision = 0.88, sensitivity = 0.88, and specificity = 0.83), and glioneuronal tumors had an accuracy of 0.83 (precision, sensitivity, and specificity = 0.83). Circumscribed astrocytic glioma and glioneuronal tumors could be discriminated from other tumor subtypes with 0.79 and 0.82 accuracy, respectively.
2024-09-30 | GSE275598 | GEO
Project description:Anaplastic lymphoma kinase (ALK) fusion variants in non-small-cell-lung cancer (NSCLC) consist of numerous dimerising fusion partners, with the most common being EML4. Clinical data suggests that the degree of treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs among the variant present in the patient tumor. Therefore, a better understanding the oncogenic signaling networks driven by different ALK-fusion variants is important. Here, we developed highly controlled doxycycline-inducible cell models bearing four different ALK fusion proteins, namely EML4-ALK-V1, EML4-ALK-V3, KIF5B-ALK, and TFG-ALK, in the context of non-tumorigenic NL20 human bronchial epithelial cells. These were complimented by patient-derived NSCLC cell lines harboring either EML4-ALK-V1 or EML4-ALK-V3 fusions. RNAseq and phosphoproteomics analysis were employed to identify dysregulated genes and hyper/hypo-phosphorylated proteins associated with ALK fusion expression. Among ALK fusion induced responses, we noted a robust inflammatory signature that included up-regulation of the Serpin B4 serine protease inhibitor in both NL20-inducible cell models and ALK-positive NSCLC patient-derived cell lines. We show that STAT3 is a major transcriptional regulator of SERPINB4 downstream of ALK fusions, along with NF-B and AP1. The upregulation of SERPINB4 promotes survival of ALK fusion expressing cells and inhibits natural killer (NK) cell-mediated cytotoxicity. In conclusion, our study reveals a novel ALK downstream survival axis that regulates Serpin B4 expression and identifies a molecular target that has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.
2023-02-16 | PXD035100 | Pride
Project description:ALK fusion positive tumor constitutes a unique entitiy in lung adenocarcionmas. We compared the allelokaryotypes of ALK fusion positive and negative tumors with SNP array to get insight into the difference of genomic background of them. Copy number analysis with Affymetrix 250K SNP arrays of 35 ALK fusion positive and 95 ALK fusion negative lung adenocarcinomas was performed with annonymous references.
2013-10-10 | E-GEOD-41536 | biostudies-arrayexpress
Project description:Anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma that accounts for 10–15% of all childhood lymphomas. Despite the observation that more than 90% of the cases show ALK-rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insight into the molecular heterogeneity within ALK-positive ALCL, we analyzed 46 ALK-positive ALCL samples by whole-exome sequencing, RNA-sequencing, and DNA methylation array analysis. Gene expression and methylation profiling consistently subclassified ALK-positive ALCL cases into two groups differentiated by ALK expression level. The ALK-low group showed enrichment pathways of the immune response and cytokine signaling and were more heavily hypermethylated than the ALK high group, which was characterized by enriched pathways of cell growth, proliferation, metabolic pathways, and large copy number change. Taken together, these findings suggest that there is molecular heterogeneity within pediatric ALK+ALCL, predicting distinct biological mechanisms that may be utilized as prognostic markers.
2023-01-02 | GSE186487 | GEO