Project description:Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. By performing RNA- and exome sequencing analyses we have discovered a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF oncogene (11%).
Project description:Intrahepatic cholangiocarcinoma (iCCA) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. By performing RNA- and exome sequencing analyses we have discovered a novel fusion event, FGFR2-PPHLN1 (16%), and damaging mutations in the ARAF oncogene (11%). Methods: mRNA and gDNA were exctracted from fresh frozen tumor tissues and corresponding normal tissue (n=8 pairs) from patients with iCCA who underwent surgical resection. RNA-seq was performed using Illumina HiSeq 2500 System with 100 nucleotide single-end reads. One sample and its paired non-tumoral tissue were eliminated from the subsequent analysis because of bad RNa quality. The same 8 paired tumors were also analyzed by whole-exome seq. Submitter confirms there are no patient privacy concerns with these data. This dataset is part of the TransQST collection.
Project description:Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC), a deadly bile duct malignancy. FGFR kinase inhibitors (FGFRi) have shown promising efficacy against FGFR2+ ICC in clinical trials, leading to the regulatory approval of the ATP-competitive FGFR inhibitors, pemigatinib and infigratinib (BGJ398), for this subset of patients who failed standard treatment . However, the objective response rate (ORR) for each FGFR inhibitor (FGFRi) studied to date in FGFR2+ ICC is <45% and disease progression invariably arises within ~6-12 months. By employing high-throughput drug screens and signaling studies, we identified signaling feedback via the EGFR pathway as a major mediator of adaptive resistance to FGFR kinase inhibition in a set of patient-derived ICC models. To further gain insights into the synergistic effects of the EGFR/FGFR combination and address the mechanisms underlying the survival pathway reactivation, we performed RNA sequencing in our FGFR-driven ICC models (ICC21 and ICC10-6). For these studies, we treated FGFR2 fusion+ ICC cell lines ICC21/ICC10-6 with four conditions (DMSO/Infigratinib/Afatinib/Combo) for 4 hours followed by RNA sequencing.
Project description:This SuperSeries is composed of the following subset Series: GSE32879: Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma [mRNA] GSE32957: Integrative Transcriptomic Profiling reveals Hepatic Stem-like Phenotype and Interplay of EMT and miR-200c in Intrahepatic Cholangiocarcinoma [miRNA] Refer to individual Series
Project description:Using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) from a high-resolution perspective.
Project description:<p>Whole exome sequencing was performed on blood and tumor specimens (collected from biopsy or rapid research autopsy) from a patient with FGFR2 fusion positive cholangiocarcinoma.</p>
Project description:We report the genertion of a gRNA library that induces mutations often found in intrahepatic cholangiocarcinoma. We use this to screen in vivo mutations that when lost act synergistically with mutant Ras. Specifically KrasG12D and NrasG12V. We have included exome sequencing of these tumours in this data set.
Project description:We report the genertion of a gRNA library that induces mutations often found in intrahepatic cholangiocarcinoma. We use this to screen in vivo mutations that when lost act synergistically with mutant Ras. Specifically KrasG12D and NrasG12V. We have included RNA sequencing of these tumours in this data set.
