This SuperSeries is composed of the SubSeries listed below.
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sex, Cell line
View SamplesPrimary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and therapy response. Yet, molecular actors and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here, we report that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumourigenesis. While a necroptosis associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes harbouring identical oncogenic drivers give rise to HCC if surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of murine HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage commitment factors, a function conserved in humans. Together, our study provides unprecedented insights into lineage commitment in liver tumourigenesis and explains molecularly why common liver damaging risk factors can either lead to HCC or ICC.
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sex
View SamplesPrimary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and therapy response. Yet, molecular actors and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here, we report that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumourigenesis. While a necroptosis associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes harbouring identical oncogenic drivers give rise to HCC if surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of murine HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage commitment factors, a function conserved in humans. Together, our study provides unprecedented insights into lineage commitment in liver tumourigenesis and explains molecularly why common liver damaging risk factors can either lead to HCC or ICC.
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sex, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Specimen part
View SamplesBACKGROUND & AIMS: We performed an integrated analysis to identify microRNAs (miRNAs) and mRNAs with altered expression in liver tumors from 3 mouse models of hepatocellular carcinoma (HCC) and human tumor tissues.
microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer.
Cell line
View Samples10 Breast cancer cell lines profiled on the Affymetrix U133 Plus 2.0 platform used in conjunction with matched DNA copy number and DNA methylation data for integrative analysis.
An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer.
Cell line
View SamplesPancreatic ductal adenocarcinoma (PDAC) is a deadly disease and a major health problem in the United States. While the cytokine TGF-ß has been implicated in PDAC development, it can exert bot pro- and anti-tumorigenic effects that are highly context dependent and incompletely understood. To better characterize the responses of neoplastic pancreas cells to TGF-ß, three-dimensional (3D) cultures of KrasG12D-expressing mouse pancreatic epithelial cells were employed. While active exposure to exogenous TGF-ß caused the KrasG12D cells to growth arrest, its subsequent removal allowed the cells to enter a hyper-proliferative, quasi-mesenchymal (QM) and progenitor-like state. This transition was highly stable and maintained by autocrine TGF-ß signaling. Transient pulses of TGF-ß have been observed during pancreatitis, a major risk factor for PDAC, and may therefore serve to convert pre-existing KrasG12D-expressing cells into QM cells. While untreated KrasG12D cells formed simple cysts in vivo, QM cells formed ductal structures resembling human PanINs. Furthermore, markers of the QM state are expressed in human PDAC and are associated with worse outcomes. These data suggest that the QM state plays a role in PDAC development and may selectively contribute to more aggressive PDAC subtypes. This work therefore provides novel molecular insights into both PDAC development and the complex role of TGF-ß in tumorigenesis. Overall design: Three technical replicates per experimental group from one isolate were analyzed by RNA sequencing
Pre-neoplastic pancreas cells enter a partially mesenchymal state following transient TGF-β exposure.
Subject
View SamplesWe report the RNA sequencing of the non-tumoral CD138- fractions of 74 MM patient BM aspirates taken at the time of diagnosis. Overall design: The sequencing of total RNA from the non-tumoral CD138- fractions of 74 MM patient BM aspirates was performed using TruSeq Stranded mRNA Sample Preparation kit on a NextSeq 500 Illumina sequencing platform (Illumina) by 5 successive runs using NextSeq 500 High Output kit v2 (Illumina) generating in average 20 million pairs of reads per sample.
Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment.
Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways.
Sex, Age, Specimen part, Disease, Disease stage
View Samples