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This Week in Nature: Apr 15, 2010

In an advance, online publication of Nature this week, researchers describe the widespread transcription they observed at neuronal activity-regulated enhancers in their genome-wide sequencing experiment. The team observed that CBP, a transcriptional co-activator, bound to around 12,000 neuronal activity-regulated enhancers; they suggest that CBP may function to recruit RNA polymerase II. "Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 mono-methylated at lysine 4," the authors write, adding that their findings report a "widespread mechanism of enhancer activation" involving RNA polymerase II binding and eRNA synthesis.

An international research team reports that the expression level of HOTAIR — a long, non-coding RNA — in primary tumors is "a powerful predictor of eventual metastasis and death." Loss of HOTAIR, the researchers write, can inhibit cancer invasiveness. "These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy," the authors conclude.

In a Perspectives piece in Nature, the International Cancer Genome Consortium presents its plans to systematically interrogate more than 25,000 cancer genomes "at the genomic, epigenomic, and trascriptomic levels" to reveal the "repertoire of oncogenic mutations, uncover traces of mutagenic influences, define clinically relevant subtypes," and more, in order to enhance the therapeutic management of cancer. In a News Feature, Heidi Ledford describes what she calls "the cancer genome challenge." Larger collaborations — and therefore "bigger numbers" — could implicate driver mutations, she says. However, "separating drivers from passengers will become even more difficult as researchers move towards sequencing entire tumor genomes," she writes.

Joe Gray of the Lawrence Berkeley National Laboratory provides commentary on the genomics of cancer metastasis. He references another research article in Nature this week, by Li Ding et al., who used massively parallel DNA sequencing methods to analyze four samples from a patient with basal-like breast cancer in order to examine the extent of mutations shared by the primary tumor and the metastasis. They found that the metastasis contained two de novo mutations and a deletion that did not exist in the primary tumor; the xenograft "retained all primary tumor mutations and displayed a mutation enrichment pattern that resembled the metastasis," Ding and colleagues write. "Of course, Ding et al. assessed the evolution of only one tumour. But if their results can be reproduced in larger studies, comparative investigations of primary tumour/xenograft/metastasis triplets might facilitate identification of genomic aberrations that play a significant part in the pathophysiology of the tumor and metastasis, and provide clues about the biological roles of these genomic regions," Gray writes.

The Scan

Study Finds Sorghum Genetic Loci Influencing Composition, Function of Human Gut Microbes

Focusing on microbes found in the human gut microbiome, researchers in Nature Communications identified 10 sorghum loci that appear to influence the microbial taxa or microbial metabolite features.

Treatment Costs May Not Coincide With R&D Investment, Study Suggests

Researchers in JAMA Network Open did not find an association between ultimate treatment costs and investments in a drug when they analyzed available data on 60 approved drugs.

Sleep-Related Variants Show Low Penetrance in Large Population Analysis

A limited number of variants had documented sleep effects in an investigation in PLOS Genetics of 10 genes with reported sleep ties in nearly 192,000 participants in four population studies.

Researchers Develop Polygenic Risk Scores for Dozens of Disease-Related Exposures

With genetic data from two large population cohorts and summary statistics from prior genome-wide association studies, researchers came up with 27 exposure polygenic risk scores in the American Journal of Human Genetics.