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1 May 2016
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Godek and colleagues showed that glioblastoma tumor-initiating cells (TIC) are a source of genetic heterogeneity due to chromosomal instability (CIN). Glioblastoma TICs exhibited an increased frequency of lagging chromosomes at anaphase compared to stable diploid cells, and FISH analysis indicated that glioblastoma TICs exhibited high levels of aneuploidy, consistent with CIN. Further, TICs exhibited extensive karyotypic diversity, and p53 DNA-binding mutations resulted in aberrant p53 function, which may prevent growth arrest following mitotic defects. These results establish a critical link between TICs and CIN, which together may promote glioblastoma through functional and genetic heterogeneity. However, increased CIN beyond a tolerable upper limit resulted in reduced proliferation, suggesting a potential therapeutic vulnerability. For details, please see the article by Godek and colleagues on page 532. - PDF Icon PDF LinkTable of Contents
ISSN 2159-8274
EISSN 2159-8290
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Clinical Response of Carcinomas Harboring the BRD4–NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628
Anastasios Stathis; Emanuele Zucca; Mohamed Bekradda; Carlos Gomez-Roca; Jean-Pierre Delord; Thibault de La Motte Rouge; Emmanuelle Uro-Coste; Filippo de Braud; Giuseppe Pelosi; Christopher A. French
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DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia
Sara E. Meyer; Tingting Qin; David E. Muench; Kohei Masuda; Meenakshi Venkatasubramanian; Emily Orr; Lauren Suarez; Steven D. Gore; Ruud Delwel; Elisabeth Paietta; Martin S. Tallman; Hugo Fernandez; Ari Melnick; Michelle M. Le Beau; Scott Kogan; Nathan Salomonis; Maria E. Figueroa; H. Leighton Grimes
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Tumor Cell–Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression
Madeleine J. Oudin; Oliver Jonas; Tatsiana Kosciuk; Liliane C. Broye; Bruna C. Guido; Jeff Wyckoff; Daisy Riquelme; John M. Lamar; Sreeja B. Asokan; Charlie Whittaker; Duanduan Ma; Robert Langer; Michael J. Cima; Kari B. Wisinski; Richard O. Hynes; Douglas A. Lauffenburger; Patricia J. Keely; James E. Bear; Frank B. Gertler
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