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This Week in PNAS: Dec 6, 2011

In the PNAS Early Edition this week, researchers at Massachusetts General Hospital present capture hybridization analysis of RNA targets, or CHART, "a hybridization-based technique that specifically enriches endogenous RNAs along with their targets from reversibly cross-linked chromatin extracts." The Mass General team applied its approach to map the Drosophila non-coding RNA roX2 genome-wide. The team reports genomic targets of roX2, demonstrating "how CHART can be used to study RNAs in a manner analogous to chromatin immunoprecipitation for proteins."

Elsewhere in the Early Edition, an international team led by investigators at the University of Nebraska Medical Center shows that PRDM1 is a tumor suppressor gene in natural killer cell lymphomas that's "inactivated by a combination of monoallelic deletion and promoter CpG island hypermethylation." When the team knocked down PRDM1 using an shRNA-based approach in normal natural killer cells, it found that those cells were positively selected for. Further, the team identifies "MYC and 4-1BBL as targets of PRDM1 in NK [natural killer] cells," and says "disruption of homeostatic control by PRDM1 may be an important pathogenetic mechanism for NKCL [natural killer cell lymphomas]."

In a paper published online in advance in PNAS this week, researchers at the University of Illinois at Chicago show that "Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in cultured cancer cells." The team says its study points to "a unique regulatory mechanism of ABCC1 expression."

The University of California, San Francisco's Yuh-Nung Jan and his team show that partial loss of one isoform of the Ets transcription factor Pointed — PntP1 — its genetic mosaic clones, or ectopic expression of the Pnt antagonist Yan, an Ets family transcriptional repressor, "results in a reduction or elimination of INPs [intermediate neural progenitor cells] and ectopic expression of Ase in type II NBs [neuroblasts]."

The Scan

Drug Response Variants May Be Distinct in Somatic, Germline Samples

Based on variants from across 21 drug response genes, researchers in The Pharmacogenomics Journal suspect that tumor-only DNA sequences may miss drug response clues found in the germline.

Breast Cancer Risk Gene Candidates Found by Multi-Ancestry Low-Frequency Variant Analysis

Researchers narrowed in on new and known risk gene candidates with variant profiles for almost 83,500 individuals with breast cancer and 59,199 unaffected controls in Genome Medicine.

Health-Related Quality of Life Gets Boost After Microbiome-Based Treatment for Recurrent C. Diff

A secondary analysis of Phase 3 clinical trial data in JAMA Network Open suggests an investigational oral microbiome-based drug may lead to enhanced quality of life measures.

Study Follows Consequences of Early Confirmatory Trials for Accelerated Approval Indications

Time to traditional approval or withdrawal was shorter when confirmatory trials started prior to accelerated approval, though overall regulatory outcomes remained similar, a JAMA study finds.