Altered telomeres in tumors with ATRX and DAXX mutations

The proteins encoded by ATRX and DAXX participate in chromatin remodeling at telomeres and other genomic sites. Because inactivating mutations of these genes are common in human pancreatic neuroendocrine tumors (PanNETs), we examined the telomere status of these tumors. We found that 61% of PanNETs displayed abnormal telomeres that are characteristic of a telomerase-independent telomere maintenance mechanism termed ALT (alternative lengthening of telomeres). All of the PanNETs exhibiting these abnormal telomeres had ATRX or DAXX mutations or loss of nuclear ATRX or DAXX protein. ATRX mutations also correlate with abnormal telomeres in tumors of the central nervous system. These data suggest that an alternative telomere maintenance function may operate in human tumors with alterations in the ATRX or DAXX genes.     

Synaptic changes in layer 2/3 underlying map plasticity of developing barrel cortex

The functional and anatomical rearrangements of cortical sensory maps accompanying changes in experience are not well understood. We examined in vivo and in vitro how the sensory map and underlying synaptic connectivity of the developing rat barrel cortex are altered when the sensory input to the cortex is partially deprived. In the nondeprived cortex, both the sensory responses and synaptic connectivity between columns were strengthened through an increase in the synaptic connection probability between L2/3 pyramids in adjacent columns. This was accompanied by a selective growth of L2/3pyramid axonal arbors between spared columns. In contrast, deprived and nondeprived cortical columns became weakly connected in their L2/3 pyramid connections.     

Atomic force microscopy of an organic monolayer

Atomic force microscope images of polymerized monolayers of n-(2-aminoethyl)-10,12-tricosadiynamide revealed parallel rows of molecules with a side-by-side spacing of approximately equal to 0.5 nanometer. Forces used for imaging (10(-8) newton) had no observable effect on the polymer strands. These results demonstrate that atomic force microscope images can be obtained for an organic system.     

Mutations in CIC and FUBP1 contribute to human oligodendroglioma

Oligodendrogliomas are the second most common malignant brain tumor in adults and exhibit characteristic losses of chromosomes 1p and 19q. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven tumors. Among other changes, we found that the CIC gene (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six cases and that the FUBP1 gene [encoding far-upstream element (FUSE) binding protein] on chromosome 1p was somatically mutated in two tumors. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.