Project description:Genome wide DNA methylation profiling of normal and tumoral urological tissues (Prostate, Kidney and Bladder). The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs in urological fresh frozzen tissue samples. Samples included morphologically normal samples of each tissue and tumor samples. Kidney: 6 normal and 17 tumor samples; Bladder: 5 normal and 25 tumor samples; Prostate: 5 Normal and 25 tumor samples.
Project description:The inter-patient variability of tumor proteomes has been investigated on a large scale but many tumors display also intra-tumoral heterogeneity (ITH) regarding morphological and genetic features. To what extent the local proteome of tumors intrinsically differs remains largely unknown. Here, we used hepatocellular carcinoma (HCC) as a model system, to quantify both inter- and intra-tumor heterogeneity across human patient specimens with spatial resolution. We first defined proteomic features that robustly distinguish neoplastic from the directly adjacent non-neoplastic tissue by integrating proteomic data from human patient samples and genetically defined mouse models with available gene expression data. We then demonstrated the existence of intra-tumoral variations in protein abundance that re-occur across different patient samples, and affect clinically relevant proteins, even in the absence of obvious morphological differences or genetic alterations. Our work demonstrates the suitability and the benefits of using mass spectrometry based proteomics to analyze diagnostic tumor specimens with spatial resolution
Project description:Glioblastoma multiforme (GBM) is a highly heterogeneous disease that shows an wide range of genetic abnormalities in comparison to other astrocytic tumors. We have extracted between 4 and 8 tumor subsamples from different areas of the malignant tissue that were at least 1cm apart. Our aim to asses the intra-tumoral heterogeneity by comparing copy number aberrations in different tumor areas to uncover important dynamics underlying GBM progression.
Project description:Glioblastoma multiforme (GBM) is a highly heterogeneous disease that shows an enourmous range of genetic abnormalities in comparison to other astrocytic tumors. Intra-patient heterogeneity in GBM has been poorly characterized both at phenotypic and genomic level. During surgical GBM resections, we have extracted between 4 and 8 tumor subsamples from different areas of the malignant tissue that were at least 1cm apart. Our aim to asses the intra-tumoral heterogeneity at the gene expression level to uncover important dynamics underlying GBM progression that may have relevant implication for treatment.
Project description:In this study gene expression profiles for 307 cases of advanced bladder cancers were compared to molecular phenotype at the tumor cell level. TUR-B tissue for RNA extraction was macrodissected from the close vicinity of the tissue sampled for immunohistochemistry to ensure high-quality sampling and to minimize the effects of intra-tumor heterogeneity. Despite excellent agreement between gene expression values and IHC-score at the single marker level, broad differences emerge when samples are clustered at the global mRNA versus tumor cell (IHC) levels. Classification at the different levels give different results in a systematic fashion, which implicates that analysis at both levels is required for optimal subtype-classification of bladder cancer.
Project description:Generation of preclinical models which recapitulate at best the extreme intra-tumoral heterogeneity (using two cell culture conditions) and inter-tumor heterogeneity between children diagnosed with high-grade gliomas.
2019-01-01 | GSE101799 | GEO
Project description:Intra-tumoral microbiome on pituitary adenomas
Project description:Given that TREX1-deficient tumor cells showed a growth delay in immunocompetent but not immunodeficient hosts, we characterize the consequences of CT26 tumor-intrinsic TREX1 loss on the host immune system by performing single-cell RNA sequencing on intra-tumoral immune cells sorted from control and TREX1 KO CT26 tumors.
Project description:Here we developed topobiologically complex mini-colons able to undergo tumorigenesis ex vivo by integrating microfabrication, optogenetic, and tissue engineering approaches. With this system, tumorigenic transformation can be spatiotemporally controlled by directing oncogenic activation through blue-light exposure, and emerging colon tumors can be tracked in real-time with single-cell resolution for several weeks without breaking the culture. These induced mini-colons display rich intra- and inter-tumoral diversity and recapitulate key pathophysiological hallmarks displayed by colorectal tumors in vivo. By fine-tuning cell-intrinsic and extrinsic parameters, mini-colons can be leveraged to unveil tumorigenic determinants, including dietary patterns, microbiota-derived metabolites, and pharmacological therapies.
