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A BAH module in BAHCC1 recognizes H3K27me3 and is involved in gene silencing. BAHCC1 is highly expressed in acute leukemia cells and contributes to their proliferation.

The NUP98–HOXA9 oncogenic fusion protein found in leukaemia undergoes phase separation in the nucleus, which helps to promote activation of leukaemic genes and to establish aberrant chromatin looping.

Wang et al. reveal a noncanonical mechanism for EZH2 in binding the oncoprotein cMyc to promote tumorigenesis, and develop a small-molecule degrader, MS177, to target both canonical and noncanonical functions of EZH2 to suppress tumour growth.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Post-neoadjuvant treatment options for patients with triple-negative breast cancer (TNBC) include the chemo-drug capecitabine but also immune checkpoint inhibitors. Here the authors report the results of a phase II study of adjuvant nivolumab, capecitabine or the combination in patients with residual TNBC.

IL-35 is an immunomodulatory cytokine, but the molecular details of its effects have remained obscure. Vignali and colleagues determine the IL-35 receptor and how its signaling pathway leads to its suppressive action.

The tumour microenvironment is low in glucose and high in the alternative metabolite lactate, which regulatory T cells are shown here to use, maintaining their ability to suppress effector immune cells.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

Chetan Bettegowda, Bert Vogelstein and colleagues identify somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors from individuals with and without neurofibromatosis. SUZ12 encodes a chromatin-modifying protein and is located adjacent to the NF1 gene on chromosome 17q11. The data support a 'three-hit' model of tumor suppression.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

A crystal structure of DNMT3A and its regulatory partner DNMT3L bound to DNA reveals the mechanistic basis for DNMT3A-mediated DNA methylation and establishes its aetiological link to human disease.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

The kinase mTOR has emerged as an important regulator of helper T cell differentiation. Powell and co-workers show that the mTOR complex mTORC1 selectively regulates T_H1 and T_H17 differentiation, whereas mTORC2 signaling is required for T_H2 differentiation.

Asymmetric division can generate effector and memory CD8⁺ T cell precursors. Powell and colleagues show asymmetric partitioning of mTORC1 activity upon CD8⁺ T cell division, which results in distinct metabolic programming of daughter T cells.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

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.

Halide salts exhibit complex radiation-induced reactions that are relevant in atmospheric chemistry, but detailed characterizations in high-level radiation fields are challenging to obtain. Here, the authors use a custom atomic force microscope to study alkali halide surface transformations in situ under 18 kGy/hr irradiation.

Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases.