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

Tunable External Cavity Semiconductor Lasers.

In this study, we propose a new method to tune the semiconductor laser lasing frequency and reducing the laser linewidth using an external deriving field. We redeveloped Floquet S-matrix which determines the transmission probabilities and the shape and position of the induced quasibound state, which accumulated incident electrons. We explored the S-matrix numerically for various system parameters. We found that the oscillating field amplitude V1 plays a curial rule in defining the profile of electrons accumulations in the quasibound state and the field’s strength made sift the position of the quasibound state. This sift in the bound state energy due field’s strength is used to tune the lasing frequency and the output of the semiconductor laser linewidth is improved by changing the field’s amplitude the deriving field. By narrowing down the electron accumulations profile the laser linewidth would be narrower