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

Sulfate (re-)cycling in the oceanic crust: Effects of seawater-rock interaction, sulfur reduction and temperature on the abundance and isotope composition of anhydrite

At mid-ocean ridges (MORs), seawater carrying dissolved sulfate (SO4) infiltrates the oceanic crust. Hydrothermal fluid emissions from such systems have much lower δ34S and sulfur is mostly present as reduced sulfide, albeit in lower total sulfur concentrations than in seawater. This has been explained by anhydrite formation and sulfate reduction based on petrographic evidence and mass balance considerations. Here, we utilize the chemical and stable isotope (δ34S, δ18O) systematics in natural anhydrite and pyrite from various locations along the submarine and on-land section of the Mid-Atlantic ridge near Iceland to quantify the key variables that control anhydrite formation and sulfate recycling in the oceanic crust. Hydrothermal anhydrite exhibited δ34S values of +20.6 ± 1.0‰ and δ18O values between +2.4 to +25.3‰. Volcanogenic anhydrite in encrustations showed δ34S values of −1.7 to +21.4‰ and δ18O values between +1.4 and +38.0‰. Hydrothermal pyrite exhibited δ34S values ranging from +3.4 and +19.7‰. Comparison of the natural dataset with results from geochemical isotope modelling revealed that δ34S and δ18O values of anhydrite and pyrite were dependent on the isotope composition of the source fluid, extent of water–rock interaction, temperature, and redox conditions. Departures of δ34S and δ18O values in anhydrite from the source fluid were caused by progressive fluid-basalt interaction where lower δ34S and δ18O values reflected a change in sources of S and O from solely fluid to basaltic origin. The δ18O values of anhydrite were additionally affected by temperature. Quantitative formation of anhydrite mainly occurred at temperatures < 150 °C, whereas at elevated temperatures (>200 °C) reduction of seawater-sulfate to H2S and subsequent pyrite precipitation were found to limit anhydrite formation. Extending our calculations to the oceanic crust revealed that the majority of seawater-sulfate is sequestered into anhydrite (3–38 Tg S yr−1) in vicinity of MORs at < 200 °C at shallow depth (<1500 m), with only a small portion of seawater-derived SO4 discharged by high-temperature hydrothermal vents (0.1–3.4 Tg S yr−1). However, sequestration of sulfur by anhydrite is not long-lasting due to retrograde dissolution of anhydrite. The removal of anhydrite upon cooling and aging of the crust may result in a return back to the oceans of 10–60% of the sulfur originally sequestered in anhydrite upon hydrothermal alteration in vicinity of MORs

The Iceland Deep Drilling Project 4.5 km deep well, IDDP-2, in the seawater-recharged Reykjanes geothermal field in SW Iceland has successfully reached its supercritical target

The Iceland Deep Drilling Project research well RN-15/IDDP-2 at Reykjanes, Iceland, reached its target of supercritical conditions at a depth of 4.5 km in January 2017. After only 6 days of heating, the measured bottom hole temperature was 426 °C, and the fluid pressure was 34MPa. The southern tip of the Reykjanes peninsula is the landward extension of the Mid-Atlantic Ridge in Iceland. Reykjanes is unique among Icelandic geothermal systems in that it is recharged by seawater, which has a critical point of 406 °C at 29.8MPa. The geologic setting and fluid characteristics at Reykjanes provide a geochemical analog that allows us to investigate the roots of a mid-ocean ridge submarine black smoker hydrothermal system. Drilling began with deepening an existing 2.5 km deep vertical production well (RN-15) to 3 km depth, followed by inclined drilling directed towards the main upflow zone of the system, for a total slant depth of 4659m (~4.5 km vertical depth). Total circulation losses of drilling fluid were encountered below 2.5 km, which could not be cured using lost circulation blocking materials or multiple cement jobs. Accordingly, drilling continued to the total depth without return of drill cuttings. Thirteen spot coring attempts were made below 3 km depth. Rocks in the cores are basalts and dolerites with alteration ranging from upper greenschist facies to amphibolite facies, suggesting that formation temperatures at depth exceed 450 °C. High-permeability circulation-fluid loss zones (feed points or feed zones) were detected at multiple depth levels below 3 km depth to bottom. The largest circulation losses (most permeable zones) occurred between the bottom of the casing and 3.4 km depth. Permeable zones encountered below 3.4 km accepted less than 5% of the injected water. Currently, the project is attempting soft stimulation to increase deep permeability. While it is too early to speculate on the energy potential of this well and its economics, the IDDP-2 is a milestone in the development of geothermal resources and the study of hydrothermal systems. It is the first well that successfully encountered supercritical hydrothermal conditions, with potential high-power output, and in which on-going hydrothermal metamorphism at amphibolite facies conditions can be observed. The next step will be to carry out flow testing and fluid sampling to determine the chemical and thermodynamic properties of the formation fluids

The Iceland Deep Drilling Project 4.5 km deep well, IDDP-2, in the seawater-recharged Reykjanes geothermal field in SW Iceland has successfully reached its supercritical target

The Iceland Deep Drilling Project research well RN-15/IDDP-2 at Reykjanes, Iceland, reached its target of supercritical conditions at a depth of 4.5 km in January 2017. After only 6 days of heating, the measured bottom hole temperature was 426 °C, and the fluid pressure was 34MPa. The southern tip of the Reykjanes peninsula is the landward extension of the Mid-Atlantic Ridge in Iceland. Reykjanes is unique among Icelandic geothermal systems in that it is recharged by seawater, which has a critical point of 406 °C at 29.8MPa. The geologic setting and fluid characteristics at Reykjanes provide a geochemical analog that allows us to investigate the roots of a mid-ocean ridge submarine black smoker hydrothermal system. Drilling began with deepening an existing 2.5 km deep vertical production well (RN-15) to 3 km depth, followed by inclined drilling directed towards the main upflow zone of the system, for a total slant depth of 4659m (~4.5 km vertical depth). Total circulation losses of drilling fluid were encountered below 2.5 km, which could not be cured using lost circulation blocking materials or multiple cement jobs. Accordingly, drilling continued to the total depth without return of drill cuttings. Thirteen spot coring attempts were made below 3 km depth. Rocks in the cores are basalts and dolerites with alteration ranging from upper greenschist facies to amphibolite facies, suggesting that formation temperatures at depth exceed 450 °C. High-permeability circulation-fluid loss zones (feed points or feed zones) were detected at multiple depth levels below 3 km depth to bottom. The largest circulation losses (most permeable zones) occurred between the bottom of the casing and 3.4 km depth. Permeable zones encountered below 3.4 km accepted less than 5% of the injected water. Currently, the project is attempting soft stimulation to increase deep permeability. While it is too early to speculate on the energy potential of this well and its economics, the IDDP-2 is a milestone in the development of geothermal resources and the study of hydrothermal systems. It is the first well that successfully encountered supercritical hydrothermal conditions, with potential high-power output, and in which on-going hydrothermal metamorphism at amphibolite facies conditions can be observed. The next step will be to carry out flow testing and fluid sampling to determine the chemical and thermodynamic properties of the formation fluids

The Iceland Deep Drilling Project at Reykjanes: Drilling into the root zone of a black smoker analog

The aim of the Iceland Deep Drilling Project is to drill into supercritical geothermal systems and examine their economic potential. The exploratory well IDDP-2 was drilled in the Reykjanes geothermal field in SW Iceland, on the landward extension of the Mid-Atlantic Ridge. The Reykjanes geothermal field produces from a <300 °C reservoir at 1 to 2.5 km depth and is unusual because it is recharged by seawater. The well was cased to 3000 m depth, and then angled towards the main up-flow zone of the system, to a total slant depth of 4659 m (~4500 m vertical depth). Based on alteration mineral assemblages, joint inversion of wireline logging, and rate of heating measurements, the bottom hole temperature is estimated to be about 535 °C. The major problem encountered during drilling was the total loss of circulation below 3 km depth and continuing to the final depth. Drilling continued without recovering drill cuttings, consequently spot coring provided the only deep rock samples from the well. These cores are characteristic of a basaltic sheeted dike complex, with hydrothermal alteration mineral assemblages that range from greenschist to amphibolite facies, hornblende hornfels, and pyroxene hornfels, allowing the opportunity to investigate water-rock interaction in the active roots of an analog of a submarine hydrothermal system. As they have not yet been sampled, the composition of the deep fluids at Reykjanes is unknown at present. Cold water is currently being injected with the aim of enhancing permeability at depth, before allowing the well to heat up prior to flow tests planned for early 2019. The well has at least two fluid feed zones, a dominant one at 3.4 km depth and a second smaller one at 4.5 km. Extensive geophysical surveys of the Reykjanes Peninsula completed recently allow correlation of geophysical signals with rocks properties and in-situ conditions in the subsurface. Earthquake activity monitored with a local seismic network during drilling the IDDP-2 drilling detected abundant small earthquakes (ML ≤ 2) within the depth range of 3–5 km. A zone at 3–5 km depth below the producing geothermal field that was generally aseismic prior to drilling, but became seismically active during the drilling. The drilling of the IDDP-2 has achieved number of scientific and engineering firsts. It is the deepest and hottest drill hole so far sited on an active mid-ocean spreading center. It penetrated an active supercritical hydrothermal environment at depths analogous to those postulated as the high temperature reaction zones feeding black smoker systems

The Iceland Deep Drilling Project at Reykjanes: Drilling into the root zone of a black smoker analog

The aim of the Iceland Deep Drilling Project is to drill into supercritical geothermal systems and examine their economic potential. The exploratory well IDDP-2 was drilled in the Reykjanes geothermal field in SW Iceland, on the landward extension of the Mid-Atlantic Ridge. The Reykjanes geothermal field produces from a <300 °C reservoir at 1 to 2.5 km depth and is unusual because it is recharged by seawater. The well was cased to 3000 m depth, and then angled towards the main up-flow zone of the system, to a total slant depth of 4659 m (~4500 m vertical depth). Based on alteration mineral assemblages, joint inversion of wireline logging, and rate of heating measurements, the bottom hole temperature is estimated to be about 535 °C. The major problem encountered during drilling was the total loss of circulation below 3 km depth and continuing to the final depth. Drilling continued without recovering drill cuttings, consequently spot coring provided the only deep rock samples from the well. These cores are characteristic of a basaltic sheeted dike complex, with hydrothermal alteration mineral assemblages that range from greenschist to amphibolite facies, hornblende hornfels, and pyroxene hornfels, allowing the opportunity to investigate water-rock interaction in the active roots of an analog of a submarine hydrothermal system. As they have not yet been sampled, the composition of the deep fluids at Reykjanes is unknown at present. Cold water is currently being injected with the aim of enhancing permeability at depth, before allowing the well to heat up prior to flow tests planned for early 2019. The well has at least two fluid feed zones, a dominant one at 3.4 km depth and a second smaller one at 4.5 km. Extensive geophysical surveys of the Reykjanes Peninsula completed recently allow correlation of geophysical signals with rocks properties and in-situ conditions in the subsurface. Earthquake activity monitored with a local seismic network during drilling the IDDP-2 drilling detected abundant small earthquakes (ML ≤ 2) within the depth range of 3–5 km. A zone at 3–5 km depth below the producing geothermal field that was generally aseismic prior to drilling, but became seismically active during the drilling. The drilling of the IDDP-2 has achieved number of scientific and engineering firsts. It is the deepest and hottest drill hole so far sited on an active mid-ocean spreading center. It penetrated an active supercritical hydrothermal environment at depths analogous to those postulated as the high temperature reaction zones feeding black smoker systems

Time-lapse characterization of hydrothermal seawater and microbial interactions with basaltic tephra at Surtsey Volcano

A new International Continental Drilling Program (ICDP) project will drill through the 50-year-old edifice of Surtsey Volcano, the youngest of the Vestmannaeyjar Islands along the south coast of Iceland, to perform interdisciplinary time-lapse investigations of hydrothermal and microbial interactions with basaltic tephra. The volcano, created in 1963-1967 by submarine and subaerial basaltic eruptions, was first drilled in 1979. In October 2014, a workshop funded by the ICDP convened 24 scientists from 10 countries for 3 and a half days on Heimaey Island to develop scientific objectives, site the drill holes, and organize logistical support. Representatives of the Surtsey Research Society and Environment Agency of Iceland also participated. Scientific themes focus on further determinations of the structure and eruptive processes of the type locality of Surtseyan volcanism, descriptions of changes in fluid geochemistry and microbial colonization of the subterrestrial deposits since drilling 35 years ago, and monitoring the evolution of hydrothermal and biological processes within the tephra deposits far into the future through the installation of a Surtsey subsurface observatory. The tephra deposits provide a geologic analog for developing specialty concretes with pyroclastic rock and evaluating their long-term performance under diverse hydrothermal conditions. Abstracts of research projects are posted at http://surtsey. icdp-online.org