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Genomic Perturbations Reveal Distinct Regulatory Networks in Intrahepatic Cholangiocarcinoma

ABSTRACT: Genomic Perturbations Reveal Distinct Regulatory Networks in Intrahepatic Cholangiocarcinoma

PROVIDER: PRJEB14974 | ENA |

REPOSITORIES: ENA

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Genomic perturbations reveal distinct regulatory networks in intrahepatic cholangiocarcinoma.

Project description:Intrahepatic cholangiocarcinoma remains a highly heterogeneous malignancy that has eluded effective patient stratification to date. The extent to which such heterogeneity can be influenced by individual driver mutations remains to be evaluated. Here, we analyzed genomic (whole-exome sequencing, targeted exome sequencing) and epigenomic data from 496 patients and used the three most recurrently mutated genes to stratify patients (IDH, KRAS, TP53, "undetermined"). Using this molecular dissection approach, each subgroup was determined to possess unique mutational signature preferences, comutation profiles, and enriched pathways. High-throughput drug repositioning in seven patient-matched cell lines, chosen to reflect the genetic alterations specific for each patient group, confirmed in silico predictions of subgroup-specific vulnerabilities linked to enriched pathways. Intriguingly, patients lacking all three mutations ("undetermined") harbored the most extensive structural alterations, while isocitrate dehydrogenase mutant tumors displayed the most extensive DNA methylome dysregulation, consistent with previous findings.ConclusionStratification of intrahepatic cholangiocarcinoma patients based on occurrence of mutations in three classifier genes (IDH, KRAS, TP53) revealed unique oncogenic programs (mutational, structural, epimutational) that influence pharmacologic response in drug repositioning protocols; this genome dissection approach highlights the potential of individual mutations to induce extensive molecular heterogeneity and could facilitate advancement of therapeutic response in this dismal disease. (Hepatology 2018).

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Gene expression profiles of bulk tumor tissues of intrahepatic cholangiocarcinoma

Project description:We report the gene expression profiles of bulk tumor tissues of intrahepatic cholangiocarcinoma

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Project description:A \"Cartes d'Identite des Tumeurs\" (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). This serie showed the heterogeneity of tumor microenvironment across intrahepatic cholangiocarcinoma.

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Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma

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Project description:Gene expression signatures for Intrahepatic cholangiocarcinoma

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Applications of Next Generation Sequencing in intrahepatic cholangiocarcinoma

Project description:We generated 100 M of high-quality sequencing reads (~10 M per sample) and catalogued the expression profiles of 1643 microRNA in each sample. The analysis showed differences of microRNAs between intrahepatic cholangiocarcinoma and normal bile duct tissues.

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RNA over-editing leads to aggressiveness of intrahepatic cholangiocarcinoma [SNP]

Project description:Alteration in RNA editing has been connected to tumor progression and many other important human diseases. However, the role of RNA editing in intrahepatic cholangiocarcinoma (ICC) remains unclear. Here we conducted a transcriptome-wide investigation in ICCs, and revealed ADAR-associated over-editing occurred uniformly in ICCs. Collectively, these results reveal a previously unrecognized role of RNA editing in malignant transformation into ICC, and ADAR1 inhibition may obviate progression and relapse of this malignancy.

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RNA over-editing leads to aggressiveness of intrahepatic cholangiocarcinoma [RNA-Seq]

2018-12-12 | GSE119336 | GEO

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Project description:The experiment was designed to display differential gene expression profiling in three human intrahepatic cholangiocarcinoma (ICC) cells upon knockdow of LKB1 tumor suppressor, by using RNAseq technology.

2014-07-29 | GSE59855 | GEO

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