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

Prophylactic intracameral levofloxacin in cataract surgery – an evaluation of safety

Cesar Ramon G Espiritu,1,2,* Joanne G Bolinao1,* 1American Eye Center, Mandaluyong, 2Department of Ophthalmology, Manila Doctors Hospital, Manila, Philippines *The authors contributed equally to this work Purpose: To evaluate posterior and anterior segment safety of an intracameral injection of levofloxacin 0.5% ophthalmic solution as prophylaxis for patients undergoing cataract extraction and intraocular lens implantation.Setting: This study was conducted at Manila Doctors Hospital, Ermita, Manila, Philippines.Design: This was a prospective interventional study.Methods: Eyes undergoing standard phacoemulsification cataract surgery with intraocular lens implantation were treated with intracameral levofloxacin 0.5% at the conclusion of surgery. Safety parameters, including best-corrected visual acuity (BCVA), endothelial cell counts, anterior chamber cells and flare, and central foveal thickness, were evaluated preoperatively and at 1 day and 1 week postoperatively.Results: A total of 50 eyes of 50 patients were included in the analysis. At 1 week postoperatively, all eyes demonstrated BCVA of 20/30 or better and 19 eyes (38%) achieved BCVA of 20/20 or better. On the first postoperative day, no corneal edema was observed, and trace to +2 cells and flare in the anterior chamber were noted in all eyes. After 1 week, all eyes had a quiet anterior chamber and endothelial cell counts decreased by an average of 225 cells/mm2, which was marginally significant (p=0.0525) when compared to other time points. Optical coherence tomography results showed no statistically significant differences between central foveal thickness measurements before and after surgery. There were also no statistically significant differences in preoperative and postoperative pachymetry. No study-related adverse events occurred.Conclusion: There were no safety concerns associated with intracameral injection of levofloxacin 0.5%, prophylactically, following cataract surgery. Further study is required to demonstrate effectiveness in endophthalmitis prevention. Keywords: intracameral levofloxacin, endophthalmitis prevention, phacoemulsification, cataract surgery, intraocular surgery, prophylaxi