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

Transarterial chemoembolisation and combined therapy

In Hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE) is the most widely used loco-regional treatment not only in the intermediate stage, but often also in early or advanced disease (\u201ctreatment stage migration\u201d), but is the least standardised, both in terms of indication and techniques. The rationale for the efficacy of transarterial therapies is that the vascularisation of HCC is, for the most part, dependent on the hepatic artery. Conventional TACE (cTACE) consists of the intra-arterial administration of a chemotherapeutic drug emulsified with Lipiodol followed by embolisation of the tumor-feeding vessels with an embolic agent (most commonly gel foam particles). Drug-eluting bead-TACE (DEB-TACE) in progressively challenging cTACE; DEB-TACE is supposed to maximise the concentration of a cytotoxic drug at the tumour level, with a slower release of the drug into tumour and minimal systemic exposure. Beads, along with their embolic properties, segregate the chemotherapeutic agent and release it over a one-week period. At present, data from the literature do not confirm the superiority of DEB-TACE over cTACE in terms of patient survival, tumour response and safety, and the choice is therefore left to the operator. Several cytotoxic drugs are administrated in both conventional and DEB-TACE. The most widely used is doxorubicin, with no evidence of its superiority over other chemotherapeutics. Transarterial embolisation (TAE) consists of a embolisation of a tumour-feeding arteries with embolic agents without adding any chemotherapeutic drugs. To date, the relative effectiveness of TACE over TAE has not been established in randomised trials. Combined treatment (radiofrequency ablation (RFA) plus TACE) is safe and effective for the treatment of unresectable patients with early/intermediate HCC exceeding 3 cm in size. Hepatic arterial infusion chemotherapy (HAIC) is frequently adopted for the treatment of locally advanced HCC in Japan, based on reports of high response rates and favourable long-term outcomes. Firm evidence of the superiority of one over the other has not yet been established. In the future, a demonstration of the survival advantage of HAIC over systemic therapies and the recognition of HAIC as one of the standards treatmens for patients with advanced HCC are expected. In intrahepatic cholangiocarcinoma (ICC), hepatic arterial therapy (HAT) seems to be a promising strategy for improving outcomes in patients with unresectable ICC. The best outcomes in termas of response and OS are reported by HAIC even it is associated with increased toxicity. Targeted treatment strategy based on patient-disease characteristic is a goal for future research. In liver metastases, liver-directed therapies have become common due to the increased complexity of hepatic surgery. Intra-arterial treatment options include TACE, TAE, HAIC and ablative techniques, such as microwave irradiation (MWI) or RF ablation. The evidence supports their use to provide salvage options when first-line treatment has failed. Although these treatments have been applied without high-level clinical evidance, they have allowed tailoring the clinical approach to the individual based on disease status and clinical condition. In patients with well-differentiated unresectable hypervascular neuroendocrine tumour (NET) liver metastases, TAE, TACE and selective transarterial radioembolisation (TARE) are the preferred choices among other treatment modalities. Transarterial embolisation and TACE generally achieve average symptomatic, biological and radiological responces of 75%, 56% and 50%, respectively with a progression-free survival of 12-18 months, with acceptable tolerance

Notes for genera – Ascomycota

Knowledge of the relationships and thus the classification of fungi, has developed rapidly with increasingly widespread use of molecular techniques, over the past 10--15 years, and continues to accelerate. Several genera have been found to be polyphyletic, and their generic concepts have subsequently been emended. New names have thus been introduced for species which are phylogenetically distinct from the type species of particular genera. The ending of the separate naming of morphs of the same species in 2011, has also caused changes in fungal generic names. In order to facilitate access to all important changes, it was desirable to compile these in a single document. The present article provides a list of generic names of Ascomycota (approximately 6500 accepted names published to the end of 2016), including those which are lichen-forming. Notes and summaries of the changes since the last edition of `Ainsworth Bisby's Dictionary of the Fungi' in 2008 are provided. The notes include the number of accepted species, classification, type species (with location of the type material), culture availability, life-styles, distribution, and selected publications that have appeared since 2008. This work is intended to provide the foundation for updating the ascomycete component of the ``Without prejudice list of generic names of Fungi'' published in 2013, which will be developed into a list of protected generic names. This will be subjected to the XIXth International Botanical Congress in Shenzhen in July 2017 agreeing to a modification in the rules relating to protected lists, and scrutiny by procedures determined by the Nomenclature Committee for Fungi (NCF). The previously invalidly published generic names Barriopsis, Collophora (as Collophorina), Cryomyces, Dematiopleospora, Heterospora (as Heterosporicola), Lithophila, Palmomyces (as Palmaria) and Saxomyces are validated, as are two previously invalid family names, Bartaliniaceae and Wiesneriomycetaceae. Four species of Lalaria, which were invalidly published are transferred to Taphrina and validated as new combinations. Catenomycopsis Tibell Constant. is reduced under Chaenothecopsis Vain., while Dichomera Cooke is reduced under Botryosphaeria Ces. De Not. (Art. 59)