Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation.

Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes. Previous studies have shown that neither c-Myc nor REST/NRSF alone could cause tumor formation. To determine whether c-Myc and REST/NRSF act together to cause medulloblastomas, we used a previously established cell line derived from external granule layer stem cells transduced with activated c-myc (NSC-M). These immortalized NSCs were able to differentiate into neurons in vitro. In contrast, when the cells were engineered to express a doxycycline-regulated REST/NRSF transgene (NSC-M-R), they no longer underwent terminal neuronal differentiation in vitro. When injected into intracranial locations in mice, the NSC-M cells did not form tumors either in the cerebellum or in the cerebral cortex. In contrast, the NSC-M-R cells did produce tumors in the cerebellum, the site of human medulloblastoma formation, but not when injected into the cerebral cortex. Furthermore, the NSC-M-R tumors were blocked from terminal neuronal differentiation. In addition, countering REST/NRSF function blocked the tumorigenic potential of NSC-M-R cells. To our knowledge, this is the first study in which abnormal expression of a sequence-specific DNA-binding transcriptional repressor has been shown to contribute directly to brain tumor formation. Our findings indicate that abnormal expression of REST/NRSF and Myc in NSCs causes cerebellum-specific tumors by blocking neuronal differentiation and thus maintaining the "stemness" of these cells. Furthermore, these results suggest that such a mechanism plays a role in the formation of human medulloblastoma.

Kenneth oder der Rückzug der großen Armee

aus dem Engl. der Miß Yonge übers. von Louise Marezoll

Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Lotte Koch, Fritz Rémond, Szenenfoto, in: Gregory Namias: Heute nacht in Samarkand

Signatur des Originals: S 36/F10849

Lotte Koch, Rollenbild, Kniestück, in: Gregory Namias: Heute nacht in Samarkand

Signatur des Originals: S 36/F10850

Fritz Rémond, Willi Umminger, Szenenbild, Doppelbildnis, in: Gregory Namias: Heute nacht in Samarkand

Signatur des Originals: S 36/F11060

Fritz Rémond, Giselle Vesco, Szenenbild, Doppelbildnis, in: Gregory Namias: Heute nacht in Samarkand

Signatur des Originals: S 36/F11061

Effects of Seed Treatments and a Soil-applied Nematicide on Corn Yields and Nematode Population Densities

Plant-parasitic nematodes are microscopic worms that feed on plants. Almost every nematode that feeds on corn is capable of feeding on many other plants. These nematode parasites are thought to be native to most Iowa soils and to have fed upon native plants before corn was grown as a cultivated crop. Population densities (numbers) of most species of plant-parasitic nematodes that feed on corn have to increase to damaging levels (called damage thresholds) before yield loss occurs.

Soybean Aphid Efficacy Evaluation

Soybean (Glycine max), grown in Iowa and most of the north central region of the United States, has not required regular insecticide use. The soybean aphid, Aphis glycines (Hemiptera: Aphididae), causes yield losses from direct plant feeding, and has been shown to transmit several plant viruses. In Iowa, soybean aphid can colonize soybean fields in June and has developed into outbreaks in July and August capable of reducing yields by nearly 40 percent.

Andrew Radde-Gallwitz, Basil of Caesarea, Gregory of Nyssa, and the Transformation of Divine Simplicity, Oxford University Press, Oxford, 2009; 261 pp. ISBN 978-0-19-957411-7.

Fil: Peretó Rivas, Rubén.