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Biallelic somatic SMARCA4 mutations in small cell carcinoma of the ovary,hypercalcemic type (SCCOHT)
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Andrey Korshunov Dominik Sturm Marina Ryzhova Volker Hovestadt Marco Gessi David T. W. Jones Marc Remke Paul Northcott Arie Perry Daniel Picard Marc Rosenblum Manila Antonelli Eleonora Aronica Ulrich Schüller Martin Hasselblatt Adelheid Woehrer Olga Zheludkova Ella Kumirova Stephanie Puget Michael D. Taylor Felice Giangaspero V. Peter Collins Andreas von Deimling Peter Lichter Annie Huang Torsten Pietsch Stefan M. Pfister Marcel Kool 《Acta neuropathologica》2014,128(2):279-289
Three histological variants are known within the family of embryonal rosette-forming neuroepithelial brain tumors. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). In this study, we performed a comprehensive clinical, pathological, and molecular analysis of 97 cases of these rare brain neoplasms, including genome-wide DNA methylation and copy number profiling of 41 tumors. We identified uniform molecular signatures in all tumors irrespective of histological patterns, indicating that ETANTR, EBL, and MEPL comprise a single biological entity. As such, future WHO classification schemes should consider lumping these variants into a single diagnostic category, such as embryonal tumor with multilayered rosettes (ETMR). We recommend combined LIN28A immunohistochemistry and FISH analysis of the 19q13.42 locus for molecular diagnosis of this tumor category. Recognition of this distinct pediatric brain tumor entity based on the fact that the three histological variants are molecularly and clinically uniform will help to distinguish ETMR from other embryonal CNS tumors and to better understand the biology of these highly aggressive and therapy-resistant pediatric CNS malignancies, possibly leading to alternate treatment strategies. 相似文献
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A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain 总被引:6,自引:0,他引:6
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Ehrenreich H Hasselblatt M Knerlich F von Ahsen N Jacob S Sperling S Woldt H Vehmeyer K Nave KA Sirén AL 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(3):862-867
Central nervous and hematopoietic systems share developmental features. We report that thrombopoietin (TPO), a stimulator of platelet formation, acts in the brain as a counterpart of erythropoietin (EPO), a hematopoietic growth factor with neuroprotective properties. TPO is most prominent in postnatal brain, whereas EPO is abundant in embryonic brain and decreases postnatally. Upon hypoxia, EPO and its receptor are rapidly reexpressed, whereas neuronal TPO and its receptor are down-regulated. Unexpectedly, TPO is strongly proapoptotic in the brain, causing death of newly generated neurons through the Ras-extracellular signal-regulated kinase 1/2 pathway. This effect is not only inhibited by EPO but also by neurotrophins. We suggest that the proapoptotic function of TPO helps to select for neurons that have acquired target-derived neurotrophic support. 相似文献
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Endothelin B receptor deficiency augments neuronal damage upon exposure to hypoxia-ischemia in vivo 总被引:1,自引:0,他引:1
Sirén AL Lewczuk P Hasselblatt M Dembowski C Schilling L Ehrenreich H 《Brain research》2002,945(1):209-149
The role of functional endothelin-B (ETB)-receptors on neuronal survival upon hypoxia-ischemia (HI) has been investigated in 14-day-old ETB-receptor-deficient spotting lethal (sl/sl) and wildtype (+/+) rats. Carotid ligation followed by exposure to 8% oxygen for 2 h produced distinct cortical and hippocampal neuronal damage. Damage severity 24 h after HI was mild to intermediate in +/+ rats whereas large cortical infarcts and profound apoptosis of the hippocampus evolved in sl/sl rats. The number of apoptotic cells in the dentate 24 h after HI amounted to 30 +/- 7 cells/0.1 mm(2) in sl/sl compared to 9 +/- 3 cells/0.1 mm(2) in wildtype rats (mean +/- S.E.M., n=10-11, P=0.0093). In-vitro hypoxia (15 h) resulted in a comparable increase in cell death in primary pure neuronal hippocampal cultures from both groups (49.8 +/- 1.6% in sl/sl, 51.4 +/- 0.9% in +/+, mean +/- S.E.M., n=5, P=0.0560). To conclude, absence of functional ETB receptors is associated with an increased susceptibility to HI in-vivo, which is not intrinsic to neurons. Antagonism of ETB receptors seems not to be desirable in ischemic stroke. 相似文献