Ena-DATASET-UH-tumorgenomics-09-08-2018-12:10:10:044-254 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001004281 | EGA |
REPOSITORIES: EGA
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Project description:Microsatellite instability (MSI), caused by defective mismatch repair, is observed in a subset of colorectal cancers (CRCs). We evaluated somatic mutations in microsatellite repeats of genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat. Expression profiling of 34 MSI colorectal cancers and 15 normal colonic mucosas was performed in 2002. Comparison of malignant and healthy tissue.
2011-03-01 | E-GEOD-24514 | biostudies-arrayexpress
Project description:Lynch syndrome (LS) patients develop DNA mismatch repair deficient tumors which generate high loads of neoantigens (neoAgs), thus constituting a well-defined population that can benefit from cancer immune-interception strategies, including neoantigen-based vaccines. Using paired whole-exome sequencing and mRNAseq of colorectal cancers (CRC) (n=13) and pre-cancers (n=61) from our LS patient cohort (N=46), we performed in-silico prediction and immunogenicity ranking of highly recurrent frameshift-neoags, followed by their in-vitro validation. We described the somatic mutation landscape in all cancers and pre-cancers, and showed that mutation burden is positively correlated with neoAgs load. Furthermore, our in-vitro validation showed a 65% validation rate of our top 100 predicted neoags. Consistent with neoAgs burden, our transcriptomic results revealed increased infiltration of CD8+ and CD4+ T-cells in microsatellite unstable samples. Overall, our neoAgs catalog and all other findings, improve our understanding of cancer development in LS and guide us towards the advancement of immunoprevention vaccine strategies.
2024-03-25 | GSE224707 | GEO
Project description:Microsatellite instability (MSI), caused by defective mismatch repair, is observed in a subset of colorectal cancers (CRCs). We evaluated somatic mutations in microsatellite repeats of genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat.
2011-03-01 | GSE24514 | GEO
Project description:Molecular and pathological landscape of heterogeneous immune subgroups of microsatellite-unstable colorectal cancers
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Project description:MRE11 Deficiency Increases Sensitivity to Poly(ADP-ribose) Polymerase Inhibition in Microsatellite Unstable Colorectal Cancers.
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Project description:VEGF-A drives TOX-dependent T cell exhaustion in anti–PD-1–resistant microsatellite stable colorectal cancers
2019-09-25 | GSE135798 | GEO
Project description:Microsatellite unstable (MSI) colorectal cancers (CRCs) are characterized by Transforming Growth Factor Beta Receptor Type 2 (TGFBR2) deficiency. TGFBR2-deficient CRCs present altered target gene and protein expression. Such cellular alterations modulate the content of CRC-derived extracellular vesicles (EVs). EVs function as couriers of proteins, nucleic acids, and lipids in intercellular communication. At a qualitative level, we have previously shown that TGFBR2 deficiency can cause overall alterations in the EV protein content. To deepen the basic understanding of altered protein dynamics, this work aimed to quantify EV protein signatures in a TGFBR2-dependent manner. Using a SILAC approach for mass spectrometry-based quantification, 48 proteins that appeared to be regulated by cellular TGFBR2 expression were identified in MSI-derived EVs. TGFBR2-primed EVs were enriched in proteasome-associated proteins, whereas TGFBR2 deficiency led to upregulation of EV proteins related to the extracellular matrix and nucleosome. Altogether, the present study emphasizes the general overlap of proteins between EVs and their parental CRC cells and highlights the pathological role of the MSI tumor driver mutation affecting TGFBR2 by altering protein landscapes of EVs. From a clinical perspective, TGFBR2-regulated quantitative differences of protein expression in EVs might nominate novel biomarkers for liquid biopsy-based MSI typing in the future.
2019-09-04 | PXD013980 | Pride
Project description:MLK3 gene mutations were described to occur in about 20% of microsatellite unstable gastrointestinal cancers and to harbor oncogenic activity. In particular, mutation P252H, located in the kinase domain, was found to have a strong transforming potential, and to promote the growth of highly invasive tumors when subcutaneously injected in nude mice. Nevertheless, the molecular mechanism underlying the oncogenic activity of P252H mutant remained elusive.In this work, we performed Illumina Whole Genome arrays on three biological replicas of human HEK293 cells stably transfected with the wild-type MLK3, the P252H mutation and with the empty vector (Mock) in order to identify the putative signaling pathways associated with P252H Our results showed that mutant MLK3 exerts its oncogenic effects by deregulating several important colorectal cancer- associated signaling pathways such as WNT, MAPK, NOTCH, TGF-M-NM-2 and P53. A more detailed analysis of the alterations affecting the WNT signaling pathway revealed a down-regulation of molecules involved in the canonical pathway, such as DVL2, LEF1, CCND1 and c-Myc, and an up- regulation of DKK, a well-known negative regulator of canonical WNT signaling, in MLK3 mutant cells. Additionally, FZD6 and FZD10 genes, known to act as negative regulators of the canonical WNT signaling cascade and as positive regulators of the planar cell polarity (PCP) pathway, a non-canonic WNT pathway, were found to be up-regulated in P252H cells. 9 samples, 2 conditions with 3 biological replicates per condition
2014-03-21 | E-GEOD-54611 | biostudies-arrayexpress
Project description:The CpG island methylator phenotype (CIMP) in colorectal tumors can be recognized by an increased frequency of aberrant methylation in a specific set of genomic loci. Because of the strong association of CIMP with high microsatellite instability (MSI-H), the identification of CIMP+ tumors within microsatellite stable (MSS) colorectal cancers may not be straightforward. To overcome this potential limitation, we have built an improved 7-loci set of methylation markers that includes CACNA1G, IGF2, RUNX3, HTR6, RIZ1, MINT31 and MAP1B. This new set of CIMP markers revealed a bimodal distribution of methylation frequencies in a group of 95 MSS colorectal cancers, which allowed a clearer separation between CIMP classes. Correlation of CIMP+ tumors with bio-pathological traits revealed significant associations with location to the proximal colon, mucinous histology and chromosomal stability. Although not statistically significant, a trend toward an adverse prognosis for CIMP+ cases was observed. Microarray analysis revealed that CIMP+ tumors are characterized by a unique expression profile, a result that confirms that CIMP+ tumors represent a distinct molecular class within MSS colorectal cancers. Moreover, our results suggest that this expression pattern may represent the molecular background for the development of CIMP+ tumors that, in turn, develop MSI when aberrant methylation occurs at the MLH1 gene promoter.
2008-01-01 | E-TABM-328 | biostudies-arrayexpress
Project description:Gene expression profiling has discriminated between sporadic microsatellite instable (MSI) and microsatellite stable (MSS) colorectal cancers (CRCs), whereas the expression pattern of familial colorectal cancer type X (FCCTX) and Lynch syndrome (LS) associated CRCs remain largely unknown. The purpose of this study is to use gene expression profiling of formalin-fixed paraffin-embedded (FFPE) tumor specimens from FCCTX, LS and sporadic CRC as a control to detect expression patterns and to identify signaling pathways differing between FCCTX and LS tumors.
2012-03-08 | GSE36335 | GEO