Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Bile Acid Receptors and Liver Cancer

Liver cancer, particularly hepatocellular carcinoma (HCC), is the third leading cause of cancer death in the world. Bile acids (BAs) are liver-produced amphipathic molecules that are required to facilitate the absorption of cholesterol, fat-soluble vitamins, and lipids in the intestine. However, BAs are also known to act as potential carcinogens and deregulation of BA homeostasis has been linked to HCC formation. Two key BA receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), were recently identified, which provides great insights into BAs’ normal physiological functions as well as their carcinogenic effects. In this review, we focus on the potential links among BAs, two BA receptors, and HCC. FXR and TGR5 not only play key roles in regulating BA homeostasis but also are essential in suppressing BAs’ carcinogenic effects on liver cancer