Search

This paper uses multiomics to profile a large cohort of meningioma samples to highlight the role of the tumor microenvironment in driving the epigenetic changes underpinning tumor classification and prediction of outcome.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Individuals who are at high risk of developing acute myeloid leukaemia can be identified years before diagnosis using genetic information from blood 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.

This study explores the relationship between telomere length and clonal hematopoiesis. Splicing factor and PPM1D gene mutations are more frequent in people with genetically predicted shorter telomere lengths, suggesting that these mutations protect against the consequences of telomere attrition.

The rarity of tumour formation despite the high proportion of cancer-driver mutations in epithelia is explained by the competitive fitness of tumour cells relative to that of surrounding mutant epithelial cells.

There is high prevalence of whole genome duplication (WGD) in high grade serous ovarian cancer. Here, the authors compare tumours with and without WGD and find that those that acquired WGD early during tumour evolution are associated with worse survival and have the lowest expression of MHC-II.

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.

A massive international effort has yielded multifaceted studies of more than 2,600 tumours from 38 tissues, generating a wealth of insights into the genetic basis of cancer.

Somatic mutational loads in cancer genomes change with chromatin domain boundaries. Different mutational processes lead to distinct somatic mutation distributions in active versus inactive domains, including during tumor evolution.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

An analysis of UK Biobank participants shows that the risk of developing different types of myeloid neoplasms can be inferred years before diagnosis. The authors integrate somatic gene mutations with blood test parameters into a predictive model, which could guide future strategies for early detection and prevention of these diseases.

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

Two papers by Kather and colleagues and Gerstung and colleagues develop workflows to predict a wide range of molecular alterations from pan-cancer digital pathology slides.

Ritter et al. present a spatial transcriptomics and deep learning-based approach named NePSTA (neuropathology spatial transcriptomic analysis) and leverage it to improve neuropathological diagnostics and enhance central nervous system tumor subtype classification.

A long-term study of 385 human donors reports that driver gene mutations and age determine the lifelong dynamics of clonal haematopoiesis

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.

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.

Here the authors find a genetic alteration in the popular “Four Core Genotypes” mouse model that is used to distinguish sex-biased phenotypes caused by sex chromosomes and gonads. This alteration increases the expression of some X-linked genes, which might confound the interpretation of the model.

Testicular germ cell tumours (TGCT) are the most common cancers in young men. Here, the authors analyse the genomic landscape of TGCT using data from the Genomics England 100,000 Genomes Project, revealing divergent evolutionary trajectories and the prevalence of human leukocyte antigen loss.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Whole-genome sequencing is used to analyse the landscape of somatic mutation in intestinal crypts from 16 mammalian species, revealing that rates of somatic mutation inversely scale with the lifespan of the animal across species.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Li-Fraumeni syndrome (LFS) is associated with pathogenic germline TP53 variants and predisposes patients to cancer; understanding the evolution and drivers of LFS-related tumours remains crucial. Here, the authors analyse 22 LFS tumours using whole-genome sequencing and reconstruct the evolution and timing of somatic driver alterations.

NanoSeq is used to detect mutations in single DNA molecules and analyses show that mutational processes that are independent of cell division are important contributors to somatic mutagenesis.

Malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division.

Whole-genome sequencing of tumours from 560 breast cancer cases provides a comprehensive genome-wide view of recurrent somatic mutations and mutation frequencies across both protein coding and non-coding regions; several mutational signatures in these cancer genomes are associated with BRCA1 or BRCA2 function and defective homologous-recombination-based DNA repair.

Multiple myeloma evolves continuously. Here the authors chronologically reconstruct driver events in multiple myeloma, noting a limited repertoire of initiating driver events that shape the evolutionary trajectory of the disease.

Whole-genome sequencing of matched serial tumours from patients identifies two key mutagenic factors (APOBEC3 and chemotherapy) and extrachromosomal DNA-forming structural variants that drive treatment resistance in urothelial cancer.

Visium spatial transcriptomics, single-nucleus RNA sequencing and co-detection by indexing are used to identify distinct spatial microregions in tumours and their microenvironment across six diverse solid cancer types.

Whole-genome sequencing of lung cancer in never smokers identifies different copy number subtypes and shows a lack of tobacco smoking signatures, even in cases exposed to secondhand smoke.

Benchmarking of tumor subclonal reconstruction algorithms finds that interalgorithm variability overwhelms intertumor variability and identifies key quality metrics.