Search

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Tumours that are deficient in mismatch-repair genes should, in theory, have higher evolvability. Here, the authors explore this theory in gastro-oesophageal tumours.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Diffuse Intrinsic Pontine Gliomas are diagnosed by sampling a small portion of the tumour. Here, using multiple samples from tumours, the authors analyse the spatial and temporal distribution of driver mutations revealing that H3K27M mutations arise first in tumorigenesis followed by a specific invariable sequence of driver mutations, which are homogeneously distributed across the tumour mass.

Current models, based on incremental changes in a single stress, have limited ability to anticipate abrupt ecosystem changes due to climate and human activities. Experiments on four models simulating ecosystems with a range of anthropogenic interactions show how much earlier abrupt change can happen.

The transcriptional program controlling the activation of cancer-associated fibroblasts (CAFs) remains to be elucidated. Here, the authors identify ANKRD1 as a mesenchymal-specific driver of CAF activation under negative direct control of androgen receptor, triggering AP-1 transcription factor complex activation.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

The hydroxylase EgIN2 contributes to triple negative breast cancers. Here, using an enzyme-substrate trapping strategy, the authors identify ASDL as a bona fide substrate of EgIN2 promoting aggressive properties of TNBC via the activation of cMYC signaling.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Grockowiak et al. explore bone marrow niche heterogeneity in myeloproliferative neoplasms, polycytemia vera and essential thrombocytemia and find JAK2-mutated hematopoietic stem cells occupying distinct niches affecting cell growth and therapy response.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

Suet Yi Leung, Mao Mao and colleagues report whole-genome sequencing of 100 gastric cancers and DNA copy number, gene expression and methylation profiling of these tumors. They identify new recurrently mutated genes and find mutation of RHOA in 14% of diffuse-type gastric cancers.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Genomic analysis of 551 esophageal adenocarcinomas identifies new driver mutations and biomarkers associated with poor prognosis. More than 50% of esophageal adenocarcinomas contain sensitizing events for CDK4/CDK6 inhibitors, thus providing an evidence base for targeted therapeutics.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

TRPA1 has been reported to contribute lung cancer adenocarcinoma (LUAD), but the mechanisms are unclear. Here the authors propose that TRPA1/FGFR2 interaction is functional in LUAD and show that astrocytes oppose brain metastasis by mediating the downregulation of TRPA1 through exosome-delivered miRNA-142-3p.

Synergies between agroecology and nutrition are explored in this Perspective, with a view towards developing a framework to transform agroecology for improved nutrition.

SCIFER detects clonal selection in whole-genome sequencing data using a population genetics model. Applied to a range of somatic tissues, SCIFER quantifies stem cell dynamics and infers clonal ages and sizes without requiring knowledge of driver events.

The interactions between climate and tectonics in active mountain ranges are complex and important. Field and geophysical data from the St Elias Range of Alaska show that glacial erosion can influence the dynamics of the lithosphere in such settings.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.

A combined modelling and tumour analysis approach is used to study the temporal and spatial patterns of subclone evolution in the TRACERx renal study. Studying the tumour shape and spatial features of clonal diversity in early-stage tumours may allow the prediction of tumour progression and patterns of subclone diversification over time.

Genome sequence data from colorectal tumours show how adenomas progress to carcinomas on the fitness landscape.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

A bookkeeping approach shows that disturbed tropical humid forests experienced net aboveground carbon loss during 1990–2020, primarily driven by small but persistent deforestation clearings owing to persistent land-use conversion without forest regrowth.

Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Different clones of a mammary tumour cell line possess differential abilities to contribute to the formation of metastasis; the expression of Serpine2 and Slp1 proteins drives vascular mimicry and metastasis to the lung, with similar associations observed in human data sets, and these proteins also function as anticoagulants, thus further promoting extravasation of tumour cells.

The extreme fields generated when a high-intensity laser or relativistic electron passes through a plasma offer the potential to accelerate particles over shorter distances than is possible with conventional accelerators. A new study suggests that driving a plasma with protons rather than electrons could be the key to generating TeV electron beams by this process.

Using deep sequencing of human carotid plaque cells from male and female patients with carotid stenosis, Sukhavasi et al. identify sex-biased cell-type-specific gene-regulatory networks and different phenotypes in smooth muscle cells, including an osteogenic phenotype in females and a chondrocytic phenotype in males.

The second Global Amphibian Assessment finds that the status of amphibians is continuing to deteriorate globally, driven predominantly by climate change, disease and habitat loss.

A cavity-array microscope is realized using intra-cavity lenses to create a two-dimensional array of over 40 modes, each coupled to a single atom in free-space.

Whole-gene sequencing of microdissected gastric glands from individuals with and without gastric cancer reveals distinct patterns of somatic mutations and provides insights into influences on the somatic evolution of the gastric epithelium.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.