The life history of 21 breast cancers.

Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.

Massive genomic rearrangement acquired in a single catastrophic event during cancer development.

Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.

China's wetland soil organic carbon pool: New estimation on pool size, change, and trajectory.

Robust estimates of wetland soil organic carbon (SOC) pools are critical to understanding wetland carbon dynamics in the global carbon cycle. However, previous estimates were highly variable and uncertain, due likely to the data sources and method used. Here we used machine learning method to estimate SOC storage and their changes over time in China's wetlands based on wetland SOC density database, associated geospatial environmental data, and recently published wetland maps. We built a database of wetland SOC density in China that contains 809 samples from 181 published studies collected over the last 20 years as presented in the published literature. All samples were extended and standardized to a 1-m depth, on the basis of the relationship between SOC density data from soil profiles of different depths. We used three different machine learning methods to evaluate their robustness in estimating wetland SOC storage and changes in China. The results indicated that random forest model achieved accurate wetland SOC estimation with R2 being .65. The results showed that average SOC density of top 1 m in China's wetlands was 25.03 ± 3.11 kg C m-2 in 2000 and 26.57 ± 3.73 kg C m-2 in 2020, an increase of 6.15%. SOC storage change from 4.73 ± 0.58 Pg in 2000 to 4.35 ± 0.61 Pg in 2020, a decrease of 8.03%, due to 13.6% decreased in wetland area from 189.12 × 103 to 162.8 × 103 km2 in 2020, despite the increase in SOC density during the same time period. The carbon accumulation rate was 107.5 ± 12.4 g C m-2 year-1 since 2000 in wetlands with no area changes. Climate change caused variations in wetland SOC density, and a future warming and drying climate would lead to decreases in wetland SOC storage. Estimates under Shared Socioeconomic Pathway 1-2.6 (low-carbon emissions) suggested that wetland SOC storage in China would not change significantly by 2100, but under Shared Socioeconomic Pathway 5-8.5 (high-carbon emissions), it would decrease significantly by approximately 5.77%. In this study, estimates of wetland SOC storage were optimized from three aspects, including sample database, wetland extent, and estimation method. Our study indicates the importance of using consistent SOC density and extent data in estimating and projecting wetland SOC storage.

An emerging coastal wetland management dilemma between mangrove expansion and shorebird conservation.

Coastal wetlands around the world have been degraded by human activities. Global declines in the extent of important habitats including mangroves, salt marsh and tidal flats necessitate mitigation and restoration efforts, however some well-meaning management actions, particularly mangrove afforestation and breakwater construction, can inadvertently cause further loss and degradation if these actions are not planned carefully. In particular, there is a potential conflict between mangrove and shorebird conservation, because mangrove afforestation and restoration may occur at the expense of bare tidal flats, which form the main foraging habitats for threatened coastal migratory shorebirds as well as supporting other coastal organisms. Here, we present several case studies that illustrate the trade-off between mangroves and bare tidal flats. To investigate whether these examples reflect an emerging broad-scale issue, we use satellite imagery to develop a detailed quantification of the change in mangrove habitat extent in 22 important shorebird areas in mainland China between 2000 and 2015. Our results indicate that 1) the extent of mangroves across all sites expanded significantly between 2000 and 2015 (p < 0.01, n = 14) while tidal flat extent in the same areas declined significantly within the same period (p < 0.01, n = 21); 2) among the 14 sites where mangroves were present, the dual threat of mangrove expansion and tidal flat loss have considerably reduced shorebird habitat in eight of these sites. To ensure effective conservation of both mangroves and shorebirds, we propose a decision tree framework for resolving this emerging dilemma between mangrove afforestation and shorebird protection, which requires careful consideration of alternative management strategies. This article is protected by copyright. All rights reserved.

Invasion of Spartina alterniflora in the coastal zone of mainland China: Control achievements from 2015 to 2020 towards the Sustainable Development Goals.

The Sustainable Development Goals (SDGs) and the Convention on Biological Diversity's 15th Conference of the Parties (CBD COP15) both emphasized the urgency of protecting biological diversity. Spartina alterniflora (S. alterniflora), as an invasive species in China, has posed severe biodiversity challenges, demanding nationwide control and management. This study aims to assess the effectiveness of S. alterniflora management during China's SDGs implementation from 2015 to 2020. Landsat images acquired in 2015 (the beginning year of SDGs), 2018, and 2020 (the end year of SDGs' targets 6.6, 14.2, 14.5, and 15.8 related to alien invasion) were applied to quantify the spatiotemporal dynamics of S. alterniflora extent. The results revealed a consistent shrinkage of S. alterniflora, with a net areal reduction of 2610 ha from 2015 to 2020, implying the effectiveness of control measures on S. alterniflora invasion. Provinces including Zhejiang, Jiangsu, and Shanghai have succeeded in controlling S. alterniflora, evidenced by the sharp reduction in S. alterniflora area by 4908 ha, 2176 ha, and 1034 ha, respectively, from 2015 to 2020. However, better management of S. alterniflora is needed in regions with more severe S. alterniflora invasion, e.g., Shandong, Fujian, and Guangdong provinces. Our results suggest that relevant policies, regulations, and ecological restoration projects implemented by national or local governments in China received satisfactory results in S. alterniflora control. Nevertheless, S. alterniflora potential utilities and its governance effectiveness should be objectively evaluated and weighed to obtain the greatest ecological benefits and promote sustainable coastal ecosystems. The results of this study are expected to provide important baseline information benefitting the formulation of coastal protection and restoration strategies in China.

Wetland changes in the Amur River Basin: Differing trends and proximate causes on the Chinese and Russian sides.

According to the United Nations Sustainable Development Goals (SDGs), understanding the extent of wetlands, their change trends and the proximate causes is important for the conservation of wetlands and endangered waterfowls. Here we studied the world's ninth largest river basin, the Amur River Basin (ARB), with a land area of 2.08 million km2. Our objectives were to address the information deficiencies of spatially explicit wetland distributions and their changes and to quantify the proximate causes of these changes in various periods in the ARB. A hybrid approach combining object-based and hierarchical decision-trees classification (HOHC) was applied to Landsat series images to obtain multitemporal land cover datasets from 1980 to 2016. Further quantitative analysis revealed that the ARB held 184,561 km2 of wetlands in 2016, accounting for 9% of the whole basin area. Among these, 59% of the wetlands were identified on the Russian side, while 40% were on the Chinese side, and 1% were on the Mongolian side. The ARB lost 22% of its wetland (52,246 km2) from 1980 to 2016, with a consistent net loss from 1980 to 2010 but an area gain from 2010 to 2016. Human activities dominated the consistent wetland losses on the Chinese side of the ARB, of which cropland expansion was the primary proximate cause of wetland loss (69%). Conversely, the wetlands on the Russian side had consistent losses from 1980 to 2010 followed by a gain from 2010 to 2016, which could be attributed to climate change. These quantified data will inform decision-making on wetland conservation and benefit scientific studies depending on spatially explicit wetland information.

COSMIC: somatic cancer genetics at high-resolution.

COSMIC, the Catalogue of Somatic Mutations in Cancer (http://cancer.sanger.ac.uk) is a high-resolution resource for exploring targets and trends in the genetics of human cancer. Currently the broadest database of mutations in cancer, the information in COSMIC is curated by expert scientists, primarily by scrutinizing large numbers of scientific publications. Over 4 million coding mutations are described in v78 (September 2016), combining genome-wide sequencing results from 28 366 tumours with complete manual curation of 23 489 individual publications focused on 186 key genes and 286 key fusion pairs across all cancers. Molecular profiling of large tumour numbers has also allowed the annotation of more than 13 million non-coding mutations, 18 029 gene fusions, 187 429 genome rearrangements, 1 271 436 abnormal copy number segments, 9 175 462 abnormal expression variants and 7 879 142 differentially methylated CpG dinucleotides. COSMIC now details the genetics of drug resistance, novel somatic gene mutations which allow a tumour to evade therapeutic cancer drugs. Focusing initially on highly characterized drugs and genes, COSMIC v78 contains wide resistance mutation profiles across 20 drugs, detailing the recurrence of 301 unique resistance alleles across 1934 drug-resistant tumours. All information from the COSMIC database is available freely on the COSMIC website.

Sensitive, selective and simultaneous electrochemical detection of multiple heavy metals in environment and food using a lowcost Fe3O4 nanoparticles/fluorinated multi-walled carbon nanotubes sensor.

Multiple heavy metals pollution in environment and food has become an ever-increasing concern and poses a serious threat towards humans and animals. To broad the multiple heavy metals detection, Fe3O4 nanoparticles, Fe3O4/multi-walled carbon nanotubes (Fe3O4/MWCNTs) and Fe3O4/fluorinated multi-walled carbon nanotubes (Fe3O4/F-MWCNTs) nanocomposites were synthesized by hydrothermal method and constructed as a simultaneous electrochemical sensor, respectively. Compared the catalytic performances of the three electrochemical sensors for the simultaneous detection of Cd2+, Pb2+, Cu2+, and Hg2+, the results showed that the Fe3O4/F-MWCNTs sensor demonstrated preponderant performance. It showed the sensitivity of 108.79, 125.91, 160.85, and 312.65 µA mM-1 cm-2 toward Cd2+, Pb2+, Cu2+, and Hg2+, respectively, which was obviously higher than that of Fe3O4/MWCNTs and Fe3O4. Additionally, the Fe3O4/F-MWCNTs sensor exhibited the wider linear detection ranges of 0.5-30.0, 0.5-30.0, 0.5-30.0, and 0.5-20.0 µM for Cd2+, Pb2+, Cu2+, and Hg2+, respectively. The limit of detections of the Fe3O4/F-MWCNTs sensor were 0.05, 0.08, 0.02, and 0.05 nM (signal to noise ratio of 3) for Cd2+, Pb2+, Cu2+, and Hg2+, respectively, fulfilling the governmental requests of the World Health Organization, China and Indian. The excellent agreement was recorded between the lowcost Fe3O4/F-MWCNTs sensor and typical methods (inductively coupled plasma mass spectrometry or atomic fluorescence spectrometry) in river water and soybean samples. Additionally, the sensor also exhibited excellent performances in selectivity, recovery, stability, and reproducibility. This proposal sensor provides a promising strategy to monitor multiple targets in the environment and food.

Simultaneous voltammetric determination of cadmium(II), lead(II), mercury(II), zinc(II), and copper(II) using a glassy carbon electrode modified with magnetite (Fe3O4) nanoparticles and fluorinated multiwalled carbon nanotubes.

A method is described for the simultaneous voltammetric determination of the heavy metal ions cadmium(II), lead(II), mercury(II), zinc(II), and copper(II) using a glassy carbon electrode (GCE) modified with magnetite (Fe3O4) nanoparticles and fluorinated multiwalled carbon nanotubes (Fe3O4/F-MWCNTs). The Fe3O4/F-MWCNT composite was synthesized by a hydrothermal method and characterized by X-ray photoelectron spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, elemental mapping, electrochemical impedance spectroscopy, and square wave stripping voltammetry. Under the optimum conditions, the electrode displays excellent response to the ions. Figures of merit for Cd(II), Pb(II), Hg(II), Zn(II), and Cu(II), respectively, include (a) high electrochemical sensitivity (29.88, 43.50, 120.86, 47.34 and 90.31 (µA µM-1 cm-2), (b) well separated peaks (at -0.70, -0.53, +0.37, -1.11 and + 0.01 V vs. Ag/AgCl); (c) low limits of detection (0.014, 0.0084, 0.0039, 0.012, and 0.0053 µM); and (d) wide linear ranges (0.048-30.0, 0.028-30.0, 0.013-32.5, 0.039-32.5, and 0.017-31.5 µM). The modified GCE displays satisfying selectivity in the presence of potentially interfering other metal ions, stability for 30 days, and reproducibility of electrodes (with a relative standard deviation between 1.2 and 4.8% for n = 6). The modified GCE was applied to the determination of several heavy metal ions in (spiked) water and rice samples, and the results agreed well with data obtained by atomic fluorescence spectrometry or inductively coupled plasma-mass spectrometry. The dramatic performance probably result from the semi-ionic C-F bond on F-MWCNTs surface with a strong negative charge, the good electrical conductivity of the F-MWCNTs and Fe3O4, the synergistic interaction between Fe3O4 and F-MWCNTs, and the nafion conductive membrane improving the stability of the modified layer and enhanced cation adsorption. Graphical abstract An environmentally-friendly, low-cost, high-throughput Fe3O4/fluorinated multi-walled carbon nanotube composite (Fe3O4/F-MWCNTs) modified glassy carbon electrode is described. It was applied to simultaneous electrochemical determination of Cd(II), Pb(II), Hg(II), Zn(II), and Cu(II) by square wave stripping voltammetry.

Rapid Invasion of Spartina Alterniflora in the Coastal Zone of Mainland China: Spatiotemporal Patterns and Human Prevention.

Given the extensive spread and ecological consequences of exotic Spartina alterniflora (S. alterniflora) over the coast of mainland China, monitoring its spatiotemporal invasion patterns is important for the sake of coastal ecosystem management and ecological security. In this study, Landsat series images from 1990 to 2015 were used to establish multi-temporal datasets for documenting the temporal dynamics of S. alterniflora invasion. Our observations revealed that S. alterniflora had a continuous expansion with the area increasing by 50,204 ha during the considered 25 years. The largest expansion was identified in Jiangsu Province during the period of 1990-2000, and in Zhejiang Province during the periods 2000-2010 and 2010-2015. Three noticeable hotspots for S. alterniflora invasion were Yancheng of Jiangsu, Chongming of Shanghai, and Ningbo of Zhejiang, and each had a net area increase larger than 5000 ha. Moreover, an obvious shrinkage of S. alterniflora was identified in three coastal cities including the city of Cangzhou of Hebei, Dongguan, and Jiangmen of Guangdong. S. alterniflora invaded mostly into mudflats (>93%) and shrank primarily due to aquaculture (55.5%). This study sheds light on the historical spatial patterns in S. alterniflora distribution and thus is helpful for understanding its invasion mechanism and invasive species management.

The landscape of cancer genes and mutational processes in breast cancer.

All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.

Mapping Forest Cover in Northeast China from Chinese HJ-1 Satellite Data Using an Object-Based Algorithm.

Forest plays a significant role in the global carbon budget and ecological processes. The precise mapping of forest cover can help significantly reduce uncertainties in the estimation of terrestrial carbon balance. A reliable and operational method is necessary for a rapid regional forest mapping. In this study, the goal relies on mapping forest and subcategories in Northeast China through the use of high spatio-temporal resolution HJ-1 imagery and time series vegetation indices within the context of an object-based image analysis and decision tree classification. Multi-temporal HJ-1 images obtained in a single year provide an opportunity to acquire phenology information. By analyzing the difference of spectral and phenology information between forest and non-forest, forest subcategories, decision trees using threshold values were finally proposed. The resultant forest map has a high overall accuracy of 0.91 ± 0.01 with a 95% confidence interval, based on the validation using ground truth data from field surveys. The forest map extracted from HJ-1 imagery was compared with two existing global land cover datasets: GlobCover 2009 and MCD12Q1 2009. The HJ-1-based forest area is larger than that of MCD12Q1 and GlobCover and more closely resembles the national statistics data on forest area, which accounts for more than 40% of the total area of the Northeast China. The spatial disagreement primarily occurs in the northern part of the Daxing'an Mountains, Sanjiang Plain and the southwestern part of the Songliao Plain. The compared result also indicated that the forest subcategories information from global land cover products may introduce large uncertainties for ecological modeling and these should be cautiously used in various ecological models. Given the higher spatial and temporal resolution, HJ-1-based forest products could be very useful as input to biogeochemical models (particularly carbon cycle models) that require accurate and updated estimates of forest area and type.

Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.

The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of ∼3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A), JARID1C (also known as KDM5C) and SETD2 (ref. 2). These genes encode enzymes that demethylate (UTX, JARID1C) or methylate (SETD2) key lysine residues of histone H3. Modification of the methylation state of these lysine residues of histone H3 regulates chromatin structure and is implicated in transcriptional control. However, together these mutations are present in fewer than 15% of ccRCC, suggesting the existence of additional, currently unidentified cancer genes. Here, we have sequenced the protein coding exome in a series of primary ccRCC and report the identification of the SWI/SNF chromatin remodelling complex gene PBRM1 (ref. 4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology.

COSMIC: exploring the world's knowledge of somatic mutations in human cancer.

COSMIC, the Catalogue Of Somatic Mutations In Cancer (http://cancer.sanger.ac.uk) is the world's largest and most comprehensive resource for exploring the impact of somatic mutations in human cancer. Our latest release (v70; Aug 2014) describes 2 002 811 coding point mutations in over one million tumor samples and across most human genes. To emphasize depth of knowledge on known cancer genes, mutation information is curated manually from the scientific literature, allowing very precise definitions of disease types and patient details. Combination of almost 20,000 published studies gives substantial resolution of how mutations and phenotypes relate in human cancer, providing insights into the stratification of mutations and biomarkers across cancer patient populations. Conversely, our curation of cancer genomes (over 12,000) emphasizes knowledge breadth, driving discovery of unrecognized cancer-driving hotspots and molecular targets. Our high-resolution curation approach is globally unique, giving substantial insight into molecular biomarkers in human oncology. In addition, COSMIC also details more than six million noncoding mutations, 10,534 gene fusions, 61,299 genome rearrangements, 695,504 abnormal copy number segments and 60,119,787 abnormal expression variants. All these types of somatic mutation are annotated to both the human genome and each affected coding gene, then correlated across disease and mutation types.

The patterns and dynamics of genomic instability in metastatic pancreatic cancer.

Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.

A small-cell lung cancer genome with complex signatures of tobacco exposure.

Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through >60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.

Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.

Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer, characterized by the presence of inactivating mutations in the VHL gene in most cases, and by infrequent somatic mutations in known cancer genes. To determine further the genetics of ccRCC, we have sequenced 101 cases through 3,544 protein-coding genes. Here we report the identification of inactivating mutations in two genes encoding enzymes involved in histone modification-SETD2, a histone H3 lysine 36 methyltransferase, and JARID1C (also known as KDM5C), a histone H3 lysine 4 demethylase-as well as mutations in the histone H3 lysine 27 demethylase, UTX (KMD6A), that we recently reported. The results highlight the role of mutations in components of the chromatin modification machinery in human cancer. Furthermore, NF2 mutations were found in non-VHL mutated ccRCC, and several other probable cancer genes were identified. These results indicate that substantial genetic heterogeneity exists in a cancer type dominated by mutations in a single gene, and that systematic screens will be key to fully determining the somatic genetic architecture of cancer.

A comprehensive catalogue of somatic mutations from a human cancer genome.

All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.

Antibody Therapies in Cancer.

Antibody-based immunotherapy has become a standard treatment for a variety of cancers. Many well-developed antibodies disrupt signaling of various growth factor receptors for the treatment of a number of cancers by targeting surface antigens expressed on tumor cells. In recent years, a new family of antibodies is currently emerging in the clinic, which target immune cells rather than cancer cells. These immune-targeted therapies strive to augment antitumor immune responses by antagonizing immunosuppressive pathways or providing exogenous immune-activating stimuli, which have achieved dramatic results in several cancers. The future of cancer therapies is likely to combine these approaches with other treatments, including conventional therapies, to generate more effective treatments.

Complex landscapes of somatic rearrangement in human breast cancer genomes.

Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.