Purpose
Gliosarcoma is a histologic variant of glioblastoma (GBM), and like GBM carries a poor prognosis. Median survival is less than one (1) year with less than 5% of patients alive after 5 years. Although there is no cure, standard treatment includes surgery, radiation and chemotherapy. While very similar to GBM, gliosarcoma exhibits several distinct differences, morphologically and molecularly. Therefore, we report a comprehensive analysis of DNA copy number changes in gliosarcoma using a cytogenomic DNA copy number (CN) microarray (OncoScan
®
).
Methods
Cytogenomic DNA copy number microarray (OncoScan
®
) was performed on 18 cases of gliosarcoma. MetaCore™ enrichment was applied to the array results to detect associated molecular pathways.
Results
The most frequent alteration was copy number loss, comprising 57% of total copy number changes. The number of losses far exceeded the number of amplifications (***, < 0.001) and loss of heterozygosity events (***, < 0.001). Amplifications were infrequent (4.6%), particularly for
EGFR
. Chromosomes 9 and 10 had the highest number of losses; a large portion of which correlated to
CDKN2A/B
loss. Copy number gains were the second most common alteration (26.2%), with the majority occurring on chromosome 7. MetaCore™ enrichment detected notable pathways for copy number gains including: HOXA, Rho family of GTPases, and EGFR; copy number loss including: WNT, NF-kß, and CDKN2A; and copy number loss of heterozygosity including: WNT and p53.
Conclusions
The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.
Recent research has identified celebration of a 21st birthday as an environmental event during which many college students engage in risky levels of alcohol consumption. The current study examined the relationship between personality and different aspects of alcohol use during 21st birthday celebrations: actual amount consumed for those who had turned 21, anticipated amount consumed for those under the age of 21, and normative beliefs regarding the amount other students consume on their 21st birthdays. Sensation seeking and impulsivity both displayed significant bivariate relationships with all three aspects of 21st birthday drinking. Personality traits did not contribute unique variance to actual 21st birthday drinking after the effects of typical alcohol consumption were accounted for in the models. Impulsivity contributed unique variance to models accounting for anticipated drinking and normative beliefs. Additional research is necessary to better understand the role personality variables play on alcohol consumption during 21st birthday celebrations.
Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset. 25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.
Phosphorus-31, cadmium-113
and mercury-199 n.m.r. spectra have been recorded for a series of O,O-dialkyldithiophosphate (dtp) and dialkyldithiocarbamate (dtc)
complexes of cadmium and mercury in dichloromethane solution. Both types of
ligand are labile on the n.m.r. time scale at room temperature, although the
exchange of dtc ligands can be slowed at low
temperatures. .The complexes interact with
tributylphosphine and tricyclohexylphosphine (pcy), but at room temperature the phosphines are also
labile. At low temperatures, however, the phosphine exchange becomes slow on
the n.m.r. time scale to allow identification of the adducts except for Cd(dtc)2 adducts with
PBu3 which are still labile at -110°C. All the data indicate that cadmium has a
lower affinity for phosphine than mercury and that dtc
ligands are more strongly bound to the metals than dtp
ligands.
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