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This Week in PLoS: Mar 1, 2010

In PLoS ONE this week, University of Washington, Seattle, researchers report their identification of novel prognostic molecular features in acute myeloid leukemia, derived from their cross-study analyses of 25 gene expression profiling studies. One third of the 4,918 reported genes were replicated in more than one study, but only 9.6 percent of those repeated were associated with AML prognostics, the authors report. The authors write that their investigation may provide insights into AML pathogenesis; their analyses are available online.

Also in PLoS ONE, a team of researchers report their investigation of the signaling pathways responsible for the flagellin-induced inflammatory and cytoprotective effects on human corneal epithelial cells. They found that corneal antimicrobial peptide production and wound repair involve a novel NF-κB-independent/EFGR-dependent pathway. The authors suggest that flagellin and its derivatives could have therapeutic applications in cytoprotection and controlling corneal infections.

Anita Hjelmeland at the Lerner Research Institute in Cleveland, Ohio, and colleagues describe their determination that A20, a NF-κB pathway regulator, is overexpressed in glioblastoma stem cells (compared to non-stem glioblastoma cells) at the protein and miRNA levels in PLoS Biology. “In silico analysis of a glioma patient genomic database indicates that A20 overexpression and amplification is inversely correlated with survival,” the authors write. They describe that, unlike with inactivating A20 mutations in lymphoma, which appears to have a tumor-suppressing effect, their data suggest that A20 may function as a tumor enhancer in gliomas. Therefore, A20 anticancer therapies should be viewed with caution, they write, because their effects likely differ among tumor types.

Collaborative research published in PLoS Genetics this week describes a genome-wide association study which revealed five loci associated with primary tooth development during infancy. Their GWAS employed data from 4,564 individuals from the 1966 Northern Finland Birth Cohort, and 1,518 individuals from the Avon Longitudinal Study of Parents and Children. The authors write that a variant within the HOXB cluster is associated with occlusion defects which require orthodontic treatment.

The Scan

Expanded Genetic Testing Uncovers Hereditary Cancer Risk in Significant Subset of Cancer Patients

In Genome Medicine, researchers found pathogenic or likely pathogenic hereditary cancer risk variants in close to 17 percent of the 17,523 patients profiled with expanded germline genetic testing.

Mitochondrial Replacement Therapy Embryos Appear Largely Normal in Single-Cell 'Omics Analyses

Embryos produced with spindle transfer-based mitochondrial replacement had delayed demethylation, but typical aneuploidy and transcriptome features in a PLOS Biology study.

Cancer Patients Report Quality of Life Benefits for Immune Checkpoint Inhibitors

Immune checkpoint inhibitor immunotherapy was linked in JAMA Network Open to enhanced quality of life compared to other treatment types in cancer patients.

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.