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Systematic satellite, ocean and atmosphere records show the pace and extent of melting in West Antarctica vary by location, with glaciers flowing to the Amundsen Sea most sensitive to atmosphere‒ocean variability atop a marine ice-sheet instability.

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.

Mass loss from the glaciers along the margins of the Greenland and Antarctic ice sheets is increasingly contributing to sea level rise. However, ice loss as a result of accelerated flow, known as dynamic thinning, is so poorly understood that its potential future contribution to sea level remains unpredictable. Here, high-resolution laser altimetry is used to map changes along these ocean margins; the results show that dynamic thinning is more important and extensive than previously thought.

Pinning-point changes over three epochs spanning the periods 1973–1989, 1989–2000 and 2000−2022 were measured, and by proxy the changes to ice-shelf thickness back to 1973–1989 were inferred.

Despite often being poorly immunogenic, some subsets of patients with hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer benefit from immunotherapy. Here, the authors present a randomised pilot clinical trial comparing a neoadjuvant run-in of either nab-paclitaxel or pembrolizumab (anti-PD-1) monotherapy, followed by the combination, in patients with stage II-III HR + /HER2- breast cancer.

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.

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.

Patient samples are often available in limited amounts, restricting the number of possible omics analyses. Here the authors present MONTE, a workflow that enables serial HLA-I and HLA-II immunopeptidome, ubiquitylome, proteome, phosphoproteome, and acetylome data collection from patient samples.

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.

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.

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.

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.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

The West Antarctic Ice Sheet is sensitive to ocean warming and contains enough ice to significantly raise sea level. Direct oceanographic measurements in the Amundsen Sea during 2010 show continuous inflow of warm water towards the thinning ice shelves in West Antarctica.

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.

Adam Bass, Gad Getz, Scott Carter and colleagues report the whole-exome sequences of 25 pairs of esophageal adenocarcinoma and Barrett's esophagus. They identify two pathways by which Barrett's esophagus can develop into esophageal adenocarcinoma.

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.

Analyses of in vivo models, cell lines and patient-derived samples show that apolipoprotein B mRNA-editing catalytic subunit 3B (APOBEC3B) not only restrains lung tumor initiation but also that its upregulation is associated with resistance to targeted therapies. This study highlights the complex and context-dependent role of APOBEC3B in lung cancer.

Adam Bass, Gad Getz and colleagues report whole-exome sequencing of 149 esophageal adenocarcinomas (EACs) and whole-genome sequencing of 15 EACs. They identify a mutational signature defined by a high prevalence of A>C transversions, as well as 26 genes mutated at high frequency in EACs.

Multiple myeloma (MM) is treated with induction chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. Here, the authors show that the presence of clonal haematopoiesis of indeterminate potential (CHIP) at time of ASCT is associated with adverse outcomes in MM patients.

Patients with BRAF^V600E-mutated colorectal cancer have encouraging overall response rates to inhibition of PD-1, BRAF and MEK, with translational analyses suggesting that induction of tumor-intrinsic programs and immune programs contributes to improved outcomes via MAPK inhibition.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

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

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Using satellite laser altimetry, basal melting of ice shelves is determined to be the main driver of Antarctic ice-sheet loss,with changing climate the likely cause.

An estimate of the mass balance components for all ice shelves in Antarctica indicates that about half of the ice-sheet surface mass gain is lost through oceanic erosion before reaching the ice front, and that the loss due to iceberg calving is about 34 per cent less than previously thought.

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.

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.

Neural mechanisms underlying cross-modal generalization of learned sensorimotor associations are not fully understood. Here authors show that mice use a specialized cortical circuit to generalize learned behaviors between vision and touch. A single region in the dorsal cortex is essential for forming abstract spatial representations that enable cross-modal flexibility.

Temozolomide therapy seems to lead to mismatch repair deficiency and hypermutation in gliomas, but not to an increase in response to immunotherapy.

An analysis of mutations from over 7,000 cancers of diverse origins reveals the diversity of mutational processes underlying the development of cancer; more than 20 distinct mutational signatures are described, some of which are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are specific to individual tumour types.

Subglacial landforms, formed by glacial processes operating over long timescales, influence ice dynamics. Here, the authors show how mega-scale landforms at an Antarctic ice stream grounding zone modulate basal water flow, causing extensive channels in the ice shelf downstream that may impact its structure.

Matthew Meyerson, Ramaswamy Govindan and colleagues examine the exome sequences and copy number profiles of 660 lung adenocarcinoma and 484 lung squamous cell carcinoma tumors. They identify novel significantly mutated genes and amplification peaks and find that around half of the tumors have at least five predicted neoepitopes.

Sandro Santagata, Gad Getz and colleagues report the discovery of a recurrent mutation in the oncogene BRAF in papillary craniopharyngiomas that does not occur in the histologically related adamantinomatous form. Their results have the potential to aid in diagnosis and treatment of these intracranial tumors.

Depth of response (CR/VGPR, MRD-) links to better outcomes, while biochemical progression predicts end-organ damage. Higher MHC-I on tumors and greater GZMB+ T cells in clonally expanded CD8+ T cells are tied to improved outcomes.

The authors show PTEN mutations, which can cause both congenital hydrocephalus and autism spectrum disorder, disrupt CSF homeostasis and brain connectivity in mice. Reducing mTORC1 activation ameliorates ventricular enlargement and neuronal deficits.

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.

Polymerase proofreading and the mismatch repair pathway maintain the fidelity of DNA replication. Here the authors show that tumors with concurrent loss of function of both pathways lead to mutation signatures that are not simply a sum of the signatures found in tumors involving single alteration.

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.

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.

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.

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.

Satellites can observe marine phytoplankton, but observations are sparse in seasonally dark, cloudy environments like the Southern Ocean. These authors use Argo floats to track the fate of phytoplankton blooms off Antarctica and determine 10% of biomass is exported, while 90% is prey to grazing.