Search

At nanometre scales, organic matter forms in soil are spatially, rather than chemically, complex, according to X-ray spectromicroscopy studies of thin sections of entire and intact free microaggregates. Organic matter forms detected at this spatial scale have no similarity to organic carbon forms of total soil.

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.

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.

Excavation in Island New Guinea reveals features associated with the Pacific Lapita cultural complex as well as sustained local cultural traditions from 3,480–3,060 years ago, contemporary with the earliest known Lapita settlements 700 km away. This supports New Guinea as a springboard for Lapita dispersal throughout the Pacific and illuminates their origins.

Introducing a phase shift between diffracted and undiffracted light from a sample is one of the oldest techniques for generating phase contrast in optical microscopy. A similar approach should help improve the contrast and clarity of images collected by scanning X-ray microscopy.

DICER is involved in the processing of miRNAs, where the RNase IIIa and IIIb domains are thought to cut the 3p and 5p hairpin arms, respectively. Here, in endometrial cancer, the authors identify an RNase IIIa mutation, which phenocopies mutations in the RNase IIIb domain.

The genetic architecture underlying Sjögren’s syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.

With continuing improvements in X-ray optics, conventional techniques for measuring their performance are finding it hard to keep up. Iterative phase-retrieval algorithms for reconstructing an optical field at the focus of an optical element could not only solve this problem, but remove the need for such optics altogether.

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.

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.

Ian Henderson and colleagues report fine-scale mapping and characterization of recombination rates in Arabidopsis thaliana. They find an enrichment of recombination hot spots overlapping transcription start and termination sites, as well as that hot spot–associated promoter regions show elevated levels of chromatin marks, including high H2A.Z, high H3K4me3 and low nucleosome density.

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 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.

William Lee and colleagues present a systematic analysis of noncoding somatic mutations in 863 tumor samples representing over 20 cancer types. They identify new mutation hotspots as well as genes with frequent mutations in their promoter regions, including WDR74 and SDHD.

Analysis of data from The Cancer Genome Atlas generates a pan-cancer network of 143 recurrent miRNA-target relationships. The identified miRNAs were frequently regulated by genetic and epigenetic alterations in cancer. The work also reveals that some miRNAs might coordinately regulate cancer pathways, such as miR-29 regulation of TET1 and TDG mRNAs, encoding components from the active DNA demethylation pathway.

In a study of children with high genetic risk aged 2 years or older, a risk score integrating pancreatic islet autoantibodies, genetic factors and family history is highly predictive of type 1 diabetes in the subsequent 8 years.

Reiner Siebert and colleagues report whole-genome, whole-exome and transcriptome sequencing of Burkitt lymphomas. They identify recurrent mutations in several genes not previously known to be mutated in Burkitt lymphoma, including ID3, FBXO11, DDX3X and RHOA.

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.