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

Copper metallogeny in the Jogimardi volcanics, Chitradurga greenstone belt

Massive volcanic-hosted sulfide deposits, within the Jogimardi volcanic suite (JVS) are Cu-rich with minor Zn and Pb and form an important early phase in the evolution of the Late Archean Chitradurga belt. The deposits are concordant stratabound lenses in the bedded mafic tuffs emplaced as submarine volcaniclastic rocks. The stratiform massive and vein-type sulfide deposits of the JVS are confined to the eastern limb of the antiform. The volcanic rock succession in the JVS consists of 85 tholeiitic basalts, 12$SiO_2$-poor variolitic andesites, and 3% of rhyolites. The basalts are quartz-normative tholeiites, not known to occur in the mid-ocean ridge basalt (MORB) environment. Unlike those of MORB, in their major, minor and REE (rare earth element) geochem., the basalts related to massive sulfide deposits are almost identical to back-arc basalts generated in an ensialic marginal basin environment. The thermal and chem. environment of ore formation are detd. based on fluid inclusions data and 34S pyrite values of individual sulfide phases. The ores were deposited in an anoxic chem. environment at $350^o$ within a pH range of 5-7, corresponding to proximal facies conditions. The stratiform sulfide ore body in the area is located in the vicinity of a fracture-controlled stringer/stockwork ore zone, a hydrothermal discharge vent in the pillowed basalts of tholeiitic compn. which confirms the proximal nature of the deposit. Uranogenic and thorogenic Pb isotope studies on the galenas of Ingladhal stratiform sulfide bodies indicate that they are not of mantle origin but derived from the basement gneisses, dated at 3 Gyr. Geol. setting, preservation of quench plagioclase textures in the pillowed basalts, and volcanogenic synsedimentary nature of the stratiform sulfide deposits indicate that the sulfides were deposited initially in the JVS prior to folding and regional greenschist-facies metamorphism

Electron Microprobe and Mineralogical Study on Cobalt Bearing Sulphide from the Kalyadi Copper Mine, Hassan District, Karnataka

Cobalt mineralisation in the Kalyadi copper-cobalt deposit in the Hassan district, Karnataka, is mostly in sulphidic banded, feldspathic cherty quartzite. Electron microprobe study conducted on sulphide concentrates from this deposit revealed that cobalt up to $3.21 wt\%$ is present exclusively in pyrite grains, whereas it is absent in chalcopyrite and arsenopyrite. From this, it infers that pyrite crystallized first, followed by chalcopyrite and arsenopyrite with most cobalt present in the mineralizing system replacing Fe in the paragenetically early-formed pyrite, thereby rendering the system deficient in cobalt during later crystallization of chalcopyrite and arsenopyrite