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Epigenetic clonality confers por prognosis in colorrectal cancer patients (technical replicates)

ABSTRACT: In CRC, 1) to identify epigenetic changes at inter-tumor and intra-tumor level, and 2) to relate intra-tumor clonality to clinical, molecular and histopathologic parameters. From 79 FFPE tumors, 3 different regions were macrodissected: invasive front (IF), digestive tract surface (DTS) and central bulk (CB). Clinical, molecular, and histopathologic parameters were stablished. Epigenetic analysis was performed using Infinium 450K beadchip (Illumina) and R statistics. Intra-tumor regions clustered together by patient. The biggest epigenetic changes were in IF vs DTS/CB. By patient, the most often divergent region was IF (49.4%) comparing with DTS and CB (25.3% in both). It did not correlate with histopathologic, molecular and clinical parameters.Epigenetic clonality is higher at intra-tumor level. The highest changes are observed in IF vs DTS/CB. No association with histopathologic, molecular, and clinical characteristics was found. Technical replicates of 12 samples previously hybridized on the Infinium HumanMethylation450 to demonstrate technique robustness.

ORGANISM(S): Homo sapiens

PROVIDER: GSE81359 | GEO | 2016/08/16

SECONDARY ACCESSION(S): PRJNA321347

REPOSITORIES: GEO

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Epigenetic clonality confers por prognosis in colorrectal cancer patients (first study)

Project description:In CRC, 1) to identify epigenetic changes at inter-tumor and intra-tumor level, and 2) to relate intra-tumor clonality to clinical, molecular and histopathologic parameters. From 79 FFPE tumors, 3 different regions were macrodissected: invasive front (IF), digestive tract surface (DTS) and central bulk (CB). Clinical, molecular, and histopathologic parameters were stablished. Epigenetic analysis was performed using Infinium 450K beadchip (Illumina) and R statistics. Intra-tumor regions clustered together by patient. The biggest epigenetic changes were in IF vs DTS/CB. By patient, the most often divergent region was IF (49.4%) comparing with DTS and CB (25.3% in both). It did not correlate with histopathologic, molecular and clinical parameters.Epigenetic clonality is higher at intra-tumor level. The highest changes are observed in IF vs DTS/CB. No association with histopathologic, molecular, and clinical characteristics was found.

2016-08-16 | GSE69550 | GEO

Epigenetic clonality confers por prognosis in colorrectal cancer patients (SNP)

2016-08-16 | GSE81362 | GEO

Epigenetic clonality confers por prognosis in colorrectal cancer patients (FOLFIRI)

2016-08-16 | GSE81472 | GEO

Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties

Project description:T cell responses within pediatric brain tumors (PBT) remain poorly understood. We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived brain tumor-infiltrating T cells to map T cell molecular profile with TCR repertoire and clonality. We demonstrate marked clonal expansion of intra-tumoral T cells and reveal their differential phenotype, transcriptional state and functional properties within brain tumors. To understand T cell responses within highly immunogenic tumors that respond to checkpoint blockers, we undertook analysis of human non-small cell lung cancer (NSCLC). We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived lung tumor-infiltrating T cells to map T cell molecular profile with clonality.

2024-01-16 | GSE221776 | GEO

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans

Project description:Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans

| PRJNA683217 | ENA

IFN gamma signaling in cytotoxic T cells restricts antitumor responses by inhibiting the maintenance and clonality of intra-tumoral stem-like T cells

Project description:IFN gamma signaling in cytotoxic T cells restricts antitumor responses by inhibiting the maintenance and clonality of intra-tumoral stem-like T cells

2022-12-16 | GSE221118 | GEO

Drosophila temperature sensitive col4a1 mutant (DTS-3) and control (OreR) comparison at permissive and at restrictive temperature

Project description:We have recently reported an allelic series of dominant, conditional, temperature-sensitive (DTS) mutations in the type IV collagen gene col4a1 in Drosophila and the onset of severe myopathy by massive degradation of striated muscle fibers, degeneration of epithelial and circular smooth muscle cells of the gut. In order to get a closer look at the molecular causes of the observed phenomena we have executed microarray experiments with the aforementioned mutant. Two growth temperatures for both DTS-3 and OreR flies with dye-swap technical control replicates.

2014-01-31 | E-GEOD-52579 | biostudies-arrayexpress

Proteomic analysis of meningiomas reveals clinically-distinct molecular patterns

Project description:Meningiomas represent one of the most common and clinically heterogeneous brain tumor types that only modestly correlate with histopathologic features. While emerging molecular profiling efforts have linked specific genomic drivers to distinct clinical patterns, the proteomic landscape of meningiomas remains largely unexplored. We utilize mass spectrometry to profile a clinically well-annotated cohort (n=69) of meningiomas stratified to span all three World Health Organization (WHO) grades and various degrees of clinical aggressiveness. In total, we quantify 3042 unique proteins and compare the patterns across different clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic (n=106 proteins, Welch’s t-test, P<0.01) and pathway-level (e.g. Notch and PI3K/AKT/mTOR) differences between convexity and skull base meningiomas. Supervised comparative analyses of different pathological grades revealed distinct patterns between benign (WHO Grade I) and atypical/malignant (WHO Grade II and III) meningiomas with classic oncogenes often enriched in higher grade lesions. Independent of WHO grade, clinically aggressive meningiomas, that rapidly recurred, also had distinctive protein patterns that converged on mRNA processing and impaired activation of the extracellular matrix naba matrisome complex. Larger sized meningiomas, and those with previous radiation exposure, also had distinct protein profiles. Collectively, we highlight distinct clinically-dependent proteomic patterns of meningiomas that may help better predict outcome and guide the development of more personalized and directed therapies.

2019-05-30 | PXD012923 | Pride

Beta-catenin in Desmoid Tumors: the role of T41A and S45F mutations on gene expression

Project description:Desmoids tumors (DTs) are rare mesenchymal infiltrative lesions that exhibit high risk of local recurrence despite surgery with negative margins. Mutations in CTNNB1 gene encoding for β-catenin are typically carried by most sporadic DTs but the evidences in support to the clinical/biological role of these mutations are contrasting. Our work is the first study specifically investigating if mutation type could influence the stability of the β-catenin structure, its affinity for α-catenin, as well as the pattern of gene expression and could in turn guide the behavior of the disease.

2018-01-11 | GSE109023 | GEO

MicroRNA expression in sporadic and FAP-associated Desmoid Tumors and correlation with beta-catenin gene mutations

Project description:Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. MicroRNAs (miRNAs) are involved in many human carcinogenesis. The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFEP) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one miRNAs were dysregulated, of which 98 miRNAs in sporadic DTs, 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The same qPCR method was used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, miR-21-3p targets, and L1 Cell Adhesion Molecule, miR-197-3p target, was also evaluated. CTNNB1 mutations associated to miRNA dysregulation could help histological diagnosis of sporadic DTs and could affect the genesis and the progression of this disease.

2017-05-01 | GSE89687 | GEO

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