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

History of Cyclodextrins

Cyclodextrins are cyclic oligosaccharides obtained by enzymatic degradation of starch. They are remarkable macrocyclic molecules that have led major theoretical and practical advances in chemistry, biology, biochemistry, health science, and agriculture. Their molecular structure is composed of a hydrophobic cavity that can encapsulate other substances to form inclusion complexes through host-guest interactions. This unique feature is at the origin of many applications. Cyclodextrins and their derivatives have a wide variety of practical applications in almost all sectors of the industry, including pharmacy, medicine, foods, cosmetics, chromatography, catalysis, biotechnology, and the textile industry.Villiers published the first reference to cyclodextrins in 1891. Since the beginning of the twentieth century, major researchers, such as Schardinger, Pringsheim, Karrer, Freudenberg, French, Cramer, Casu, Bender, Saenger, Nagai, Szejtli, and Pitha, have paved the history of the cyclodextrins. Several time periods have marked their history. After their discovery and characterization from 1891 to 1911, there has been a period of doubt and disagreement from 1911 to 1935. Then, the 1935–1950 exploration period was marked by structural results on the “Schardinger dextrins.” In 1949, Cramer introduced the cyclodextrin-based nomenclature. Research between 1950 and 1970, the period of maturation, focused on conformations and spectroscopic data of cyclodextrins and their inclusion complexes, with applications in catalysis and as enzyme models. Finally, the period of use has been ongoing since 1970 and has seen cyclodextrins find many industrial applications. Cyclodextrins have then found many industrial applications, initially in the pharmaceutical and food sectors. In 1984, the first chromatographic columns were commercialized. At that time, many cyclodextrin-based catalysts were developed for biomimetic chemistry and other applications such as artificial enzymes. Currently, more than 2000 publications on cyclodextrins are published each year.In this chapter, we present a historical overview of the discovery, development, and applications of cyclodextrins