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Whole-genome doubling induces the loss of segregation of chromatin compartments, and can lead to tumour-promoting epigenetic and transcriptional modifications.

Computational algorithms to infer chromatin sub-compartments and compartment domains require high-resolution Hi-C maps. Here the authors present Calder, an algorithm that can infer sub-compartments and compartment domains with variable resolution Hi-C data, and they apply it to more than a hundred Hi-C experiments to study sub-compartment repositioning.

CellCharter is a flexible, platform-agnostic method for identifying cell niches in spatially resolved data. Analysis of lung cancers demonstrates the importance of considering spatial information, exemplified by a neutrophil-associated niche that correlates with an aggressive cancer cell state and patient prognosis.

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.

Oncogenic gain-of-function EZH2 mutations alter gene–promoter interactions and lead to silencing 1,034 of genes within topologically associating domains, thus resulting in inactivation of multiple tumor-suppressor genes.

Computational analysis of over 9,000 cancer genomes, coupled with functional validation in cell lines, highlights combinations of mutations required for tumor progression. This integrated approach provides a framework to stratify patients on the basis of interdependent genetic aberrations.

Discerning and analyzing the mutational patterns that arise in the cancer genome can provide essential information on the process of tumorigenesis. An analytical framework and web-based tool now aim to aid in mutational signature assignment for improved tumor stratification.

Choosing the most effective anti-cancer therapy is difficult due to the high degree of tumour cell and tumour microenvironment heterogeneity. Here, the authors develop a platform for the generation of patient-derived B-cell lymphoma models (termed lymphomoids) which maintain the lymphoid tissue architecture, to enable drug screening.

Enhancer–promoter three-dimensional interactions at oncogenic loci are modulated by H3K27ac dynamics. Enhancer hijacking mediated by chromosomal translocations leads to distinct chromatin states, intrachromosomal interactions and allele-specific gene expression.

Breast-to-brain metastasis is enabled by activation of an N-methyl-d-aspartate receptor, which is achieved via the formation of pseudo-tripartite synapses between cancer cells and glutamatergic neurons.

Parsa et al. report a mechanism of lymphoma initiation involving cooperation of BCL2 and increased activity of the metabolic enzyme SHMT2, which imparts changes in DNA and histone methylation.

The tumor microenvironment is central to the immunogenicity of tumors. Ho and colleagues show that activity of the mitochondrial protein UCP2 in tumors enhances their immunogenicity through the recruitment of dendritic cells and reprogramming of this microenvironment.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

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 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.

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.

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.

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 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.

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.

T cells generated from human iPSCs engineered to express a chimeric antigen receptor display innate lymphoid properties and inhibit tumor growth in mice.

Chris Sander and colleagues have extracted significant functional events from 12 tumor types. Tumors can be classified as being driven largely by either mutation or copy number changes, and, within this division, subclasses of cross-tissue patterns of events are discerned that suggest sets of combinatorial therapies.

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.