Genomic alterations in diverse cell types at different sites in the body give rise to hundreds of different forms of cancer and the ways in which these changes give rise to tumors with different biology, pathology and treatment strategies are beginning to be characterized. The Cancer Genome Atlas Research Network has catalogued the aberrations in the DNA, chromatin and RNA of the genomes of thousands of tumors relative to matched normal cellular genomes and have analyzed their epigenetic and protein consequences. Here, the Pan-cancer initiative examines the similarities and differences among the genomic and cellular alterations found in the first dozen tumor types to be profiled by TCGA. This first look across cancer offers new tools in genomics and bioinformatics and the prospect of repurposing targeted therapies directed by the molecular pathology of the tumors in addition to their clinical classification.

The iCOGS Focus highlights 13 papers in genetic epidemiology from the COGS consortium, representing a significant advance in our understanding of genetic susceptibility to breast, ovarian and prostate cancer.

iCOGS collection provides a collaborative model

Celiac disease is an intestinal inflammatory disorder that occurs in genetically predisposed individuals and causes intolerance to wheat protein gluten and related proteins (prolamines) that are contained in barley and rye. Histologically, the small bowel mucosa in celiac disease shows villous atrophy (lost of villi), crypt hyperplasia and lymphocyte infiltration. To allow better understand the histological damage that occurs during mucosal changes Marsh proposed a series of stages to aid diagnostics: Marsh I represents lymphocytic enteritis, Marsh II represents lymphocytic enteritis with crypt hyperplasia, and Marsh III represents partial (a), subtotal (b) and total (c) villous atrophy. These changes are accompanied by a gradual increase in the number of T cells and activation of immunoregulatory counteractions in the diseased mucosa. The March 2011 special issue on celiac sprue and mucosal immunity presents some of the latest advances in celiac disease diagnostics; the web focus further expands our understanding of this inflammatory disorder through a collection of recent articles from across Springer Nature.

Gene silencing through RNA interference (RNAi) has become the tool of choice for genome-scale, high-throughput analyses of gene function and has had a tremendous impact on science and drug discovery. Now, RNAi libraries targeting whole genomes or functionally related pathways permit systematic screens for clinically relevant components of cellular networks. Advances in rational design, sequence selection strategies and delivery options have substantially improved the utility of short interfering RNA (siRNA), short hairpin RNA (shRNA) and microRNA (miRNA) tools for screening.

Individual genomes vary, not only in sequence, but in both their structural organization and in the number of sequence copies they contain. We now have the technology to understand the mechanisms by which genomes diverge, and to investigate the consequences of copy number variation for gene expression and clinical phenotypes. With sponsorship from Agilent Technologies, we present a Focus on copy number variation highlighting the complementary roles of paired-end sequencing and oligonucleotide array technology in research discovery.

The 'Year of the Rat' offers a mixture of commentaries and primary research papers showcasing the increasing power of rat genetics and its contribution to understanding complex traits. This focus is freely available for three months.

MicroRNAs (miRNAs) — an abundant class of small non–protein–coding regulators of gene expression — play an important role in tumorigenesis and, depending on their targets, can function as tumour suppressors or oncogenes. Crucially, miRNA–expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment.

We are pleased to announce the publication of a supplement devoted to structural variation in the human genome.

The sequencing of the equivalent of an entire human genome for $1,000 has been announced as a goal for the genetics community, and new technologies suggest that reaching this goal is a matter of when, rather than if. What then? In celebration of its upcoming 15th anniversary, Nature Geneticsasked prominent geneticists to weigh in on this question: what would you do if this sequencing capacity were available immediately?

microRNAs are a considerable part of the transcriptional output of the genomes of plants and animals, they regulate a large part of their transcriptomes, and they serve important regulatory functions in widespread biological activities.

Milestones in Gene Expression is a collaborative project involving six journals - Nature,Nature Cell Biology,Nature Genetics,Nature Reviews Genetics,Nature Reviews Molecular Cell BiologyandNature Structural & Molecular Biology- and celebrates almost 50 years of discoveries in the field of transcription and chromatin.