Study of pediatric hepatocellular carcinoma caused by bile salt export pump deficiency

Study ID Alternative Stable ID Type
EGAS00001000749 Other

Study Description

Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. We mapped the acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters, which expose hepatocytes to bile salts and cause the onset of chronic inflammation that develops into cancer. In both human and mouse cancer genomes we found few somatic point mutations with no impairment of cancer genes, but instead massive gene amplification and rearrangements. This genomic landscape differs greatly from that of virus- and alcohol-associated liver cancer. Copy number gains preferentially occurred at late stages of cancer development and frequently targeted the MAPK signaling pathway, and in particular direct regulators of JNK. The pharmacological inhibition of JNK retarded cancer progression in the mouse. Our study demonstrates that intrahepatic cholestasis leading to hepatocyte exposure to bile acids and inflammation promotes cancer through genomic ... (Show More)

Study Datasets 2 datasets.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
Whole exome sequencing of 6 HCCs and matched background liver in children with bile salt export pump deficiency.
Illumina HiSeq 2000 12
SNP array of 7 HCCs and matched background liver in children with bile salt export pump deficiency
Illumina HumanOmniExpress-12 v1. 14

Who archives the data?

There are no publications available