Additional file 2: of Landscape of gene fusions in epithelial cancers: seq and ye shall find

Clinical trials involving gene fusions in epithelial cancers. (PDF 287 kb

Additional file 1: of Landscape of gene fusions in epithelial cancers: seq and ye shall find

Recurrent gene fusions in epithelial cancers. Summary of recurrent gene fusions in epithelial carcinoma across different tissues. a Gene fusions with common 5′ and 3′ genes. b Multiple 5′ partners with common 3′ genes. c Common 5′ gene partners with multiple 3′ genes. (DOCX 25 kb

Analysis of the Tau-Associated Proteome Reveals That Exchange of Hsp70 for Hsp90 Is Involved in Tau Degradation

The microtubule associated protein tau (MAPT/tau) aberrantly accumulates in 15 neurodegenerative diseases, termed tauopathies. One way to treat tauopathies may be to accelerate tau clearance, but the molecular mechanisms governing tau stability are not yet clear. We recently identified chemical probes that markedly accelerate the clearance of tau in cellular and animal models. In the current study, we used one of these probes in combination with immunoprecipitation and mass spectrometry to identify 48 proteins whose association with tau changes during the first 10 min after treatment. These proteins included known modifiers of tau proteotoxicity, such as ILF-2 (NFAT), ILF-3, and ataxin-2. A striking observation from the data set was that tau binding to heat shock protein 70 (Hsp70) decreased, whereas binding to Hsp90 significantly increased. Both chaperones have been linked to tau homeostasis, but their mechanisms have not been established. Using peptide arrays and binding assays, we found that Hsp70 and Hsp90 appeared to compete for binding to shared sites on tau. Further, the Hsp90-bound complex proved to be important in initiating tau clearance in cells. These results suggest that the relative levels of Hsp70 and Hsp90 may help determine whether tau is retained or degraded. Consistent with this model, analysis of reported microarray expression data from Alzheimer’s disease patients and age-matched controls showed that the levels of Hsp90 are reduced in the diseased hippocampus. These studies suggest that Hsp70 and Hsp90 work together to coordinate tau homeostasis

Additional file 1: of Medulloblastoma therapy generates risk of a poorly-prognostic H3 wild-type subgroup of diffuse intrinsic pontine glioma: a report from the International DIPG Registry

Table S1. Treatment details for primary medulloblastoma. Table S2. Multivariate analysis of overall survival for primary and radiation-associated DIPGs. Table S3. Sequencing of radiation-associated DIPGs. Figure S1. Immunohistochemical staining for H3K27 M of positive and negative control pediatric high-grade gliomas. Figure S2. Diagnosis and management of case 2, which included non-standard treatment for medulloblastoma. Figure S3. Diagnosis and management of case 3, which included standard therapy for medulloblastoma. (DOCX 5366 kb