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González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

‘Treatment resistance is common in ovarian high grade serous carcinoma, often leading to relapse. Here, the authors leverage shallow whole genome and panel sequencing of 276 patients with available diagnostic and relapse samples and show high concordance of copy number and mutation status.

Integrative analysis of copy number and gene expression in 2,000 primary breast tumours with long-term clinical follow-up revealed putative cis-acting driver genes, novel subgroups and trans-acting aberration hotspots that modulate subgroup-specific gene networks.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

Response to treatment in high grade serous ovarian carcinoma (HGSOC) is highly variable. Here, the authors leverage a radiogenomic model to predict neoadjuvant chemotherapy response in HGSOC, including clinical data, medical imaging, and blood-based biomarkers such as CA-125 and ctDNA features.

The prevalence of centrosome amplification (CA) and the genomic landscape of chromosomal instability in high-grade serous ovarian carcinoma (HGSOC) remain to be explored. Here the authors suggest CA as a potential driver of tumour evolution and a biomarker for treatment response in HGSOC.

The authors identify copy number signatures from shallow whole-genome sequencing of high-grade serous ovarian cancer (HGSOC) cases. HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in genomic aberration.

Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma. Here we show that identification of clonal somatic copy number alterations in frequently amplified cancer genes could inform therapeutics for precision medicine.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Here the authors show that chromosomal instability signatures can predict resistance to anthracycline-, taxane- and platinum-based chemotherapeutics in breast, ovarian and prostate cancer and sarcoma. Validation is performed through emulation of phase 2 and 3 clinical trials using real-world data.

Whether ovarian cancer originates in the ovary or the surrounding tissues is a focus of debate. Work in mice now shows that stem cells that replenish the ovarian surface epithelium can be the initiators of this cancer. See Letter p.241

Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.

Large-scale screens of chemical and genetic vulnerabilities in cancer are typically limited to simple readouts of cell viability. Here, the authors develop a method for profiling post-perturbation transcriptional responses across large pools of cancer cell lines, enabling deep characterization of shared and context-specific responses.

As part of the modENCODE initiative, which aims to characterize functional DNA elements in D. melanogaster and C. elegans, this study uses RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages of the fruitfly. Among the results are scores of new genes, coding and non-coding transcripts, as well as splicing and editing events.

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

Golub and colleagues identify the phosphate exporter XPR1 as a therapeutic vulnerability in ovarian and uterine cancers, and show that phosphate efflux inhibition reduces tumor cell viability through accumulation of intracellular phosphate.

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

Copy number signatures characterize different types of chromosomal instability and predict drug response.

A large-scale transcriptome analysis in Drosophila melanogaster, across tissues, cell types and conditions, provides insights into global patterns and diversity of transcription initiation, splicing, polyadenylation and non-coding RNA expression.

A genomic and transcriptomic analysis identifies molecular features associated with long-term survival in ovarian cancer. Exceptional survival was heterogeneous across the cohort, suggesting that it is likely the function of multiple cell-intrinsic and microenvironmental factors working in combination.

A proof of principle study shows that by exome sequencing of cell-free circulating DNA from cancer patient plasma samples, the genomic evolution of metastatic cancers and the acquisition of resistance in response to therapy can be tracked over time.

A pediatric cancer dependency map generated with genome-scale CRISPR–Cas9 loss-of-function screens in 82 pediatric cancer cell lines highlights genetic dependencies across a range of tumor types.

The heterogeneity of androgen receptor (AR) gene alterations across metastases in prostate cancer remains unresolved. Here, the authors characterise AR genomic complexity across spatially separated lethal metastases from 10 prostate cancer patients and investigate how AR alterations evolve.

The original Cancer Cell Line Encyclopedia (CCLE) is expanded with deeper characterization of over 1,000 cell lines, including genomic, transcriptomic, and proteomic data, and integration with drug-sensitivity and gene-dependency data.

Most testicular germ-cell tumours are exquisitely sensitive to platinum-based chemotherapies, but little is known about why 10% are resistant. Here, the authors explore the potential underlying mechanisms by probing the genomic landscape of platinum-resistant disease.

Immunogenomic analyses of advanced high-grade serous ovarian cancer samples before and after neoadjuvant chemotherapy show that the tumor–immune microenvironment is intrinsically heterogeneous and that chemotherapy induces local immune activation.

Abnormal PR interval duration is associated with risk for atrial fibrillation and heart block. Here, van Setten et al. identify 44 PR interval loci in a genome-wide association study of over 92,000 individuals and find genetic overlap with QRS duration, heart rate and atrial fibrillation.

Uniform processing and detailed annotation of human, worm and fly RNA-sequencing data reveal ancient, conserved features of the transcriptome, shared co-expression modules (many enriched in developmental genes), matched expression patterns across development and similar extent of non-canonical, non-coding transcription; furthermore, the data are used to create a single, universal model to predict gene-expression levels for all three organisms from chromatin features at the promoter.

Stabilization of DNA quadruplex structures (G4) is lethal for cells with a compromised DNA repair pathway. Here, the authors show that CX-5461, a small molecule in clinical trials as RNA polymerase inhibitor, has G4-stablization properties and can be repurposed to target DNA repair-defective cancers cells.

Keith Ligon, Adam Resnick, Rameen Beroukhim and colleagues identify MYB-QKI fusions in angiocentric gliomas and show that these rearrangements promote tumorigenesis through activation of MYB by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of QKI.

In this work, a nanobody based intermolecular strain sensor was used to follow the mechanical strain in the nuclear lamina. The results indicate that mechanical state of the nuclear lamina is not only affected by the cell contractility, but also chromatin packing.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

Findings over the last year or so have built the case that microRNAs might contribute to cancer. Three studies now definitively show this to be the case and also suggest that these small RNAs could be used to categorize tumors.

The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

This Opinion article outlines a set of research priorities, based on discussions held at the 2015 Helene Harris Memorial Trust Ovarian Cancer Action meeting, that the authors believe will reduce incidence and improve outcomes for women with high-grade serous ovarian cancer.

This Opinion article outlines nine major recommendations for improving our understanding of ovarian cancer and the outcomes of women with this group of diseases.

Circulating tumour DNA (ctDNA) analysis has the potential to improve prognostication, molecular profiling and disease monitoring in patients with cancer. This Review summarizes recent advances, potential applications in cancer research and personalized oncology, and the introduction of ctDNA into clinical use.