{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Francesca D."],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000191"],"host":["EGA"],"description":["EGA DAC EGAC00001000191"],"repository":["EGA"],"email":["francesca.ciccarelli@kcl.ac.uk"],"pubmed_abstract":["Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. Here we map acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters, which expose hepatocytes to bile salts and cause chronic inflammation that develops into cancer. In both human and mouse cancer genomes, we find few somatic point mutations with no impairment of cancer genes, but massive gene amplification and rearrangements. This genomic landscape differs from that of virus- and alcohol-associated liver cancer. Copy-number gains preferentially occur at late stages of cancer development and frequently target the MAPK signalling pathway, and in particular direct regulators of JNK. The pharmacological inhibition of JNK retards cancer progression in the mouse. Our study demonstrates that intrahepatic cholestasis leading to hepatocyte exposure to bile acids and inflammation promotes cancer through genomic modifications that can be distinguished from those determined by other aetiological factors."],"pubmed_title":["Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency."],"pubmed_authors":["Iannelli Fabio F, Collino Agnese A, Sinha Shruti S, Radaelli Enrico E, Nicoli Paola P, D'Antiga Lorenzo L, Sonzogni Aurelio A, Faivre Jamila J, Buendia Marie Annick MA, Sturm Ekkehard E, Thompson Richard J RJ, Knisely A S AS, Natoli Gioacchino G, Ghisletti Serena S, Ciccarelli Francesca D FD"],"name_synonyms":["Carcinomas, BRIC2, ABCB11 progressive familial intrahepatic cholestasis, Spgp, study, Carcinoma, Bsep, type 2, Liver, progressive familial intrahepatic cholestasis caused by mutation in ABCB11, Adult Liver Cancers, Hepatocellular carcinoma, Liver Cancer, Hepatoma, BSEP deficiency, adult primary hepatocellular carcinoma, Liver Cancers, Cell Carcinoma, ABC16, Liver Cell, Cancers, adult hepatoma, PGY4, Adult, Hepatomas, severe ABCB11 deficiency., Liver Cell Carcinoma, Hepatocellular Carcinoma, Lith1, SPGP, Cell Carcinomas, BSEP, HCC, Liver Cell Carcinomas, PFIC2, Hepatocellular, Adult Liver Cancer, 2, Adult Liver, cholestasis, PFIC-2, Hepatocellular Carcinomas, progressive familial intrahepatic cholestasis type 2, progressive familial intrahepatic, Cancer"],"pubmed_title_synonyms":["Carcinomas, Bile Acid, Acid, Salts, Carcinoma, Bile Acids, Liver, Drives, Adult Liver Cancers, Hepatocellular carcinoma, Liver Cancer, Hepatoma, Gallensaeuren, Salt, Bile Salts, Bile Salt, adult primary hepatocellular carcinoma, Liver Cancers, Gene, Cell Carcinoma, bile acids, Liver Cell, Bile acid, Cancers, adult hepatoma, Adult, Hepatomas, Gallensaeure, Liver Cell Carcinoma, Hepatocellular Carcinoma, Cell Carcinomas, Bile salt, HCC, 5beta-bile acids, Liver Cell Carcinomas, Amplification, Hepatocellular, Adult Liver Cancer, Acids, Adult Liver, Hepatocellular Carcinomas, 5beta-bile acid, bile salts., Cancer, Bile"],"pubmed_abstract_synonyms":["Salts, Bile Acids, Materials, Inflammations, SAPKa, single-organism developmental process, methionine aminopeptidase activity, primary tumour of the liver, Laboratory, ERK/MAPK cascade, Mus domesticus, postnatal development, Bile Salt, Hepatocyte, \"Intrahepatic cholestasis (finding)\" EXACT [SNOMEDCT_2005_07_31:4637005], growth and development, adult hepatoma, Tumor, hepatic, Hepatomas, 1-hydroxyethane, BSK, Bsk, Intrahepatic, Liver Cell Carcinoma, House Mouse, hepatocellular carcinoma plus intrahepatic cholangiocarcinoma, primary liver cancer, alcohol, Mutations, Bile salt, Hepatic Cell, RGD1563855, Alkohol, Virus, 2, parenchymal liver cell, SAPK1, JNK-46, peptidase M activity, Bile, adenomas, not specified as primary or secondary, rabGAPLP, DRCTNNB1A, L-methionine aminopeptidase activity, Hepatic Cancer, Man (Taxonomy), inflammatory response, Genomes, DBSK/JNK, Junk, Gallensaeuren, Salt, adult primary hepatocellular carcinoma, HLD5, RabGAP-5, Swiss Mice, AI849689, Adult, Aethanol, hepatic cancer, [CH2Me(OH)], Biliary Stases, Hepatocellular Carcinoma, Dehydrated ethanol, Bile Duct Obstruction, malignant neoplasm, RUSC3, MAPKKK cascade during sporulation, c-Jun, Malignancies, Cancer of the Liver, house mouse, associated, hepatic neoplasm, Cholestases, Tumors, spiritus vini, liver Cancer, Bile Acid, Carcinoma, D-junk, Liver, dJNK, Modern, MYH-associated polyposis, mouse, Cancer of Liver, autosomal recessive familial adenomatous polyposis, Bile Salts, primary cancer of liver, Intrahepatic Biliary Stasis, Maps, liver Cancers, MLS, Liver Cell, Ethyl alcohol, not genetically inherited, Hepatic Cells, JNK21B1/2, Benign, HCC, Liver Neoplasm, Genetic Materials, Adult Liver, [OEtH], 5beta-bile acid, Genetic Material, autosomal recessive, Carcinomas, Mus musculus, Acid, RUTBC3, EtOH, Hepatoma, parenchymal hepatic cell, mice, non-resectable primary hepatic malignant neoplasm, Swiss Mouse, Benign Neoplasms, Bile acid, Biliary Stasis, alcohol etilico, Methylcarbinol, human, RABGAP5, domesticus, Malignant Neoplasms, neoplasm of liver, DJNK, Material, MAPK signalling, multiple colorectal, Cells, Hepatocellular Cancers, Intrahepatic Cholestases, Cancer of liver, Cistron, Animal Viruses, Mouse, Acids, Hepatocellular Carcinomas, Innate, BSK/DJNK, Malignant Neoplasms., HYCC1, Inflammatory Response, NEOPL LIVER, human being, resectable malignant neoplasm of the liver, Neoplasms, etanol, Benign Neoplasm, number, Cell Carcinoma, Gene, bile acids, Hepatic Neoplasm, Malignant, presence, Intrahepatic Biliary Stases, Human, Cell Carcinomas, Aethylalkohol, liver, Prkm8, Homo sapiens, Liver Cell Carcinomas, House, Core Genome, Adult Liver Cancer, Mus musculus domesticus, Animal, Mice, Man, familial adenomatous polyposis, MAP, DmelCG5680, primary, DJNK/bsk, MCOPS7, study, Animal Virus, Genetic, Viruses, Liver Cancer, Malignancy, primary malignant neoplasm of Liver, Swiss, familial adenomatous polyposis 2, MAPK signaling, Accessory Genome, Cancer of the liver, JNK21B1|2, Liver Cancers, Hepatic Neoplasms, inflammation, malignant neoplasm of liver, c-Jun N-terminal kinase activity, PRKM8, Gallensaeure, autosomal recessive multiple colorectal adenomas, Neoplasias, C2H5OH, malignant hepato-biliary neoplasm, Resectable malignant neoplasm of Liver, primary malignant neoplasm of liver, Innate Inflammatory Response, Intrahepatic Cholestasis, Hepatic, Chronic, CCHL, Cancer, SAPK1c, JNK, Jnk, MUTYH-Associated Polyposis, Malignant Neoplasm, Hepatic Cancers, JNK3alpha1, liver parenchymal cell, primary tumor of the liver, Point Mutations, Cistrons, Pangenome, Cell, bile salts, development, count in organism, JNK/SAPK, jnk, MT, JNK1, Mus, D-JNK, JNK1A2, Neoplasm, Amplification, alcool ethylique, Zoophaginae, Mutation, primary cancer, ca liver - primary, Adult Liver Cancers, Hepatocellular carcinoma, postnatal growth, House Mice, Cancers, MYH-Associated Polyposis, malignant tumor of liver, malignant tumor, Laboratory Mice, SAPK1C, hydroxyethane, Pan-genome, Ca liver - primary, 5beta-bile acids, Point, CG5680, Innate Inflammatory Responses, Modern Man, cardinality, Hepatocellular, LIVER NEOPL, MAP syndrome, growth, Laboratory Mouse, Hepatocellular Cancer, Neoplasia, FAP2, colorectal adenomatous polyposis"],"additional_accession":[]},"is_claimable":false,"name":"Study of pediatric hepatocellular carcinoma with BSEP deficiency","description":"Data Access Committee EGAC00001000191","dates":{"output":"2025-1-9"},"accession":"EGAC00001000191","cross_references":{"TAXONOMY":["9606"],"pubmed":["24819516"],"EGA":["EGAS00001000749","EGAD00010000560","EGAD00001000811"]}}