This peculiar tumor is likely to present with unusual biological features that could be discovered by transcriptomic profiling. Malouf et al. performed gene expression arrays in 14 patients with fibrolamellar carcinoma (FLC). In comparison selleck to normal liver and HCC arising in noncirrhotic liver, FLC has a distinct gene expression signature
with activation of the ERBB2 pathway and overexpression of several neuroendocrine genes. An unsupervised clustering of gene expression profiles distinguished two subtypes of FLC with different clinical features. Recently, a chimeric transcript leading to deregulated activation of protein kinase A was reported in FLC. With these observations, our understanding of the molecular changes occurring in FLC increases dramatically and may lead to therapeutic advances. (HEPATOLOGY; 2014;59:2228–2237.) Ubiquitination PI3K inhibitor is a posttranslational modification that alters the cellular location or function of proteins or targets proteins for proteasomal degradation. Ubiquitin is activated by ubiquitin-activating enzyme (E1), then transferred to ubiquitin-conjugating enzyme (E2), which works in concert with ubiquitin-protein ligase (E3), which recognizes the proteins to be ubiquitinated. Jiang et al. sequenced the exome of a dysplastic nodule, two HCCs, and peripheral blood from the same patient and identified mutations in the UBE3C gene, an E3 ligase. They found
mutations in this gene in 16% of HBV-induced HCCs. It was also found that HCC cell lines expressing less UBE3C undergo epithelial-mesenchymal transition. Whether expression of a mutated UBE3C Rolziracetam has similar effects has not been tested. Finally, overexpression of UBE3C was associated with HCC recurrence. Even if the role of the mutations in the UBE3C gene remains to be investigated, this work adds to the evidence that ubiquitination is involved in hepatocarcinogenesis. (HEPATOLOGY; 2014;59:2216–2227.) COP9 signalosome regulates the enzymatic complex responsible for ubiquitination. COP9 is composed of several proteins; among them, COPS5 removes NEDD8 adducts from Cullin-RING ubiquitin ligase. These ligases control other factors
responsible for licensing sites of DNA replication. Panattoni et al. report that, in mice lacking hepatocellular COPS5, regenerative stimuli result in DNA rereplication, meaning that the genome is replicated more than once per cell cycle. This triggers replicative stress, which leads to cell-cycle arrest, polyploidy, and apoptosis. This striking phenotype could be rescued in mice lacking the cyclin-dependent kinase inhibitor 2A gene. Conversely, acute expression of c-Myc partially recapitulates the replicative stress observed in the absence of COPS5. This work highlights the complex interactions between DNA replication and ubiquitin ligases. (HEPATOLOGY; 2014;59:2331–2343.) “
“With population movements, the hydatid cyst may be increasingly encountered in non-sheep-farming countries.