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Axonal injury, induced in the white matter by expansion of early tumour cells, is a key driver of glioblastoma progression.

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.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Whole-genome sequencing of more than 2,000 colorectal carcinoma samples provides a highly detailed view of the genomic landscape of this cancer and identifies new driver mutations.

A central question in cancer research is how specific driver mutations are acquired and maintained during cancer development. Here Temko et al. use public sequencing data to infer the effect of mutation and selection on a set of driver mutations and suggest that selection frequently dominates.

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.

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.

Papillary renal cell carcinoma (pRCC) is a subtype of kidney cancer characterized by highly variable clinical behaviour. Here the authors sequence either the genomes or exomes of 31 pRCCs and identify several genes in sub-clones and large copy number variants in major clones that may be important drivers of pRCC.

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.

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.

The mechanisms that determine whether fibrosis occurs during chronic skin inflammation are poorly understood. Here, the authors show that chronic inflammatory skin diseases characterized by skin fibrosis share activation of EGFR-STAT1 signaling in pathologic fibroblasts as a disease defining signaling mechanism.

Peter Campbell, Mel Greaves and colleagues use exome and whole-genome sequencing to characterize somatic mutations in childhood acute lymphoblastic leukemias with the ETV6-RUNX1 fusion gene. They find that RAG-mediated deletions are the dominant mutational process.

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.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Most cancer genomics studies have focused on identifying the most important somatic mutations ('major drivers') that promote tumour growth. However, many cancer-associated mutations might instead have relatively weak tumour-promoting effects. This Opinion article highlights the existence of these mutations (termed 'mini drivers') and the functional effects that they might have.

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.

Ex vivo normothermic machine perfusion has been proposed to protect donor kidneys. Here, the authors show that red blood cell-based human kidney perfusion and associated hemolysis contribute to iron accumulation, ferroptosis, and kidney injury.

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

Researchers reveal widespread, newly formed seafloor seeps along Antarctica’s Ross Sea coast. Methane-rich flows alter local ecosystems and may influence warming. The drivers remain unknown, warranting coordinated study.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours. Here the authors report that BCA and BCAC patients possess distinct genomic profiles despite histopathological similarities, and identify a recurrent FBXW11 missense mutation (p.F517S) which leads to accumulation of β-catenin in BCA and higher expression of Wnt/β-catenin targets.

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.

Much effort has recently been devoted to understanding the genomics of breast cancer. In this study, the authors integrate somatic mutation data with previously published copy number aberration and gene expression information for nearly 2,500 breast cancer samples.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

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.

Truncation of exon 18 of FGFR2 (FGFR2^ΔE18) is a potent driver mutation in mice and humans, and FGFR-targeted therapy should be considered for patients with cancer expressing stable FGFR2^ΔE18 variants.

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.

Oesophageal adenocarcinoma is often treated with chemotherapy before surgery. Here, the authors sequence cancer samples before and after chemotherapy and examine how the genome changes, focusing on changes in driver gene mutations and differential clonal evolution between good and poor responders.

Healthy tissues from individuals with germline mutations in POLE or POLD1 show increased mutational burden, suggesting that normal cells are capable of tolerating high mutation rates.

Simulated annual wheat yields during 1889–2020 show that, since the 1990s, Indian Ocean Dipole has replaced El Niño Southern Oscillation as the dominant climate driver across most of the Australian wheatbelt. The occurrences of more positive Indian Ocean Dipole events in recent decades resulted in severe yield reductions.

Sulfur isotope excursions in skeletal collagen samples from Eurasia suggest rapidly changing biogeochemical processes across the region from about 30,000 to 15,000 years ago, potentially related to changing permafrost conditions.

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

In this study, Yang et al. compile a global dataset to uncover the degree to which plants coordinate root and seed traits. They report a global positive correlation between root diameter and seed size, driven by dual roles of arbuscular mycorrhiza in phosphorus uptake and pathogen defence.

MouseGoggles is a miniaturized virtual reality (VR) headset for mice that provides an improved immersive experience compared with existing VR equipment. MouseGoggles can also be combined with pupil tracking and has been applied in combination with calcium imaging or electrophysiological recordings.

A global land surface phenology map predicts complex geographical discontinuities in flowering phenology, genetic divergence and harvest seasonality across a range of taxa.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Patients with metastatic cancers of unknown primary (CUP) are currently unable to gain access to drugs through standard of care or clinical trials. Here, the authors perform whole-genome and transcriptome sequencing (WGTS) on 72 patients with CUP and demonstrate the feasibility of using WGTS to determine the specific cancer types of CUP, thereby clinically benefiting patients with CUP.

REVOLVER uses transfer learning on multi-region tumor sequencing data to jointly infer tumor evolution models in multiple individuals and to detect repeated evolutionary trajectories. Repeated evolution can be used to stratify the cohort.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Greenhouse gas emissions of major commodity field crops are of increasing interest to diverse stakeholders. A carbon footprint analysis following the ISO 14067 standard reveals key drivers of, and differences in, emissions for selected field crop production and transport to market between Canada and other countries.

Exciton diffusion plays a role in many optoelectronic devices. In some materials, this migration cannot be detected using photoluminescence. Mullenbachet al. use photovoltage measurements to extract the diffusion length in organic photovoltaic cells, and examine a series of non-luminescent materials.

Ian Tomlinson and colleagues report the identification of germline variants in POLE and POLD1 that are susceptibility alleles for colorectal cancer. POLE and POLD1 encode DNA polymerases that function in DNA replication.

Bruzos et al. analyze >6,800 samples of Cerastoderma edule, generate a reference genome and follow the evolution of bivalve transmissible neoplasia that infects them. They find two lineages that show genomic instability but also long-term tolerance.