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The transcription factor BRN2 regulates melanoma migration and invasion, but its role during melanoma initiation is unclear. Here the authors show that BRN2 is a haplo-insufficient tumour suppressor that positively regulates PTEN expression and in the context of BRAF mutation and heterozygous PTEN, BRN2 loss promotes melanoma initiation and progression.

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.

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.

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 genetic diversity of wild relatives of domesticated crops can be useful for developing more productive, nutritious and resilient crop varieties. A comparison of the modelled diversity of crop wild relatives with their representation in gene banks suggests that a systematic effort is needed to improve their conservation and availability for use in plant breeding.

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.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Kiourtis et al. show that liver senescence triggers senescence and dysfunction in other organs through TGFβ secretion from the liver.

The processes that regulate melanoblast migration during development are also thought to be involved in melanoma metastasis. Here, Prex1 null mice are shown to have a melanoblast migration defect and, when crossed to a mouse model of melanoma, are resistant to metastasis, suggesting a role for Prex1 in metastatic melanoma.

Kang et al. reveal structural and functional differences in mitochondria across the hepatic lobule. Mitochondrial distinct phosphoproteome influences their functions highlighting how nutrient availability helps to shape mitochondria zonation.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

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.

On amino acid deprivation TFEB translocates from the cytoplasm to the nucleus. Here the authors identify a nuclear export signal in TFEB that requires dual phosphorylation at the S142 ERK/mTORC1 and S138 GSK3β sites, and further show glucose limitation drives nuclear accumulation of TFEB and inhibits GSK3β via an mTORC2-AKT dependent mechanism.

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 this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.

Clancy et al. delineate a pathway for pre-miRNA delivery into nascent extracellular vesicles released from tumour cells and show that shed vesicles contain machinery allowing cell-free pre-miRNA processing.

ADGRF1 is an adhesion GPCR that signals when a bound ligand induces liberation of an intramolecular tethered agonist. Here, the authors show that ADGRF1 can signal though all major G protein classes and identify a structural basis for Gq selectivity.

Regulatory miRNAs have significant therapeutic potential. Here the authors developed a screen to identify small molecule drugs that modulate miRNome profiles in human neurons and validated cardiac glycosides as inducers of the neuroprotective miR-132.

As proof of principle, an analysis using a suite of human-aligned immunocompetent mouse models of hepatocellular carcinoma identifies a promising therapeutic candidate, cladribine, which acts in a highly effective subtype-specific manner in combination with standard-of-care therapy.

Genetic and genome-wide analysis of a catalytically deficient SETDB1-like enzyme, MET-2, in Caenorhabditis elegans reveals that MET-2 promotes transcriptional silencing and fertility through both H3K9 methylation and focus formation, which blocks histone acetylation.

Unusual weather encourages discussion of weather modification. Colin Norman reports on the debate in the western United States

Alzheimer’s disease is associated with changes in astrocytes. Here the authors investigated the astrocyte translatome associated with amyloid-ß and tau pathology.

Remotely sensed NDVI data and contemporary field data from 84 grasslands on 6 continents show increasing divergence in aboveground plant biomass between sites in different bioclimatic regions.

Mi-2β is an enzyme of the chromodomain helicase DNA family with roles in chromatin assembly, genomic stability and gene repression. Here the authors report that Mi-2β promotes immune evasion by activating EZH2 methylation and that loss of Mi-2β or its inhibition promote anti-tumor immune responses in preclinical melanoma models.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Sharks and rays are vital coral reef species. This study shows that nearly two thirds (59%) of the 134 coral-reef associated species are threatened with extinction. The main cause of their decline is found to be overfishing, both targeted and unintentional, and extinction risk is greater for larger species found in nations with higher fishing pressure and weaker governance.

A boreal conifer is advancing northwards into Arctic tundra, with this treeline advance facilitated by climate warming together with winter winds, deeper snow and increased soil nutrient availability.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Here the authors show that contemporary SARS-CoV-2 Omicron variants are evolving towards the upper respiratory tract while causing less severe disease in the lung. The more antigenically distinct variant JN.1 fails to transmit in the male hamster model and causes reduced pathology.

Efficient therapeutic strategies to target mutant-p53 cancers are needed. Here, the authors demonstrate the molecular mechanism through which mutant-p53 tumours are susceptible to oxidative damage and propose a potential strategy for targeting such cancers by inhibiting the SLC7A11-glutathione axis.