Search

Glioblastoma multiforme (GBM) encompasses brain malignancies marked by phenotypic and transcriptional heterogeneity thought to render these tumors aggressive, resistant to therapy, and inevitably recurrent. However, little is known about how the spatial organization of GBM genomes underlies this heterogeneity and its effects. Here, we compiled a cohort of 28 patient-derived glioblastoma stem cell-like lines (GSCs) known to reflect the properties of their tumor-of-origin; six of these were primary-relapse tumor pairs from the same patient. We generated and analyzed kbp-resolution chromosome conformation capture (Hi-C) data from all GSCs to systematically map >3,100 standalone and complex structural variants (SVs) and the >6,300 neoloops arising as a result. By combining Hi-C, histone modification, and gene expression data with chromatin folding simulations, we explain how the pervasive, uneven, and idiosyncratic occurrence of neoloops sustains tumor-specific transcriptional programs via the formation of new enhancer-promoter contacts. We also show how even moderately recurrent neoloops can help us infer patient-specific vulnerabilities. Together, our data provide a resource for dissecting GBM biology and heterogeneity, as well as for informing therapeutic approaches.

Object It is generally believed that the outcome of traumatic brain injury is not improved by decompressive craniectomy in patients older than 30–50 years. A literature search was performed to assess the level of evidence with respect to the effect of age on outcome in these cases. Methods References were identified by PubMed searches of journal articles published between 1995 and December 2008. The inclusion criteria were as follows: 1) clinical series including adults; and 2) focus on age as a prognostic factor. Technical notes and laboratory investigations were excluded. Results Fourteen English-language articles were finally selected. In 5 of the 14 studies, the authors performed no statistical analysis. In 6 studies they concluded that age was not significantly related to outcome (with 1 of these studies showing a correlation between age and outcome only after 65 years). Three studies showed a correlation between age and outcome. Conclusions With respect to age and effectiveness of decompressive craniectomy, there are no robust data to establish any degree of core evidence and the referred age thresholds are arbitrary.