DTI Abnormalities Related to Glioblastoma: A Prospective Comparative Study with Metastasis and Healthy Subjects.

(1) Background: Glioblastoma multiforme (GBM) shows complex mechanisms of spreading of the tumor cells, up to remote areas, and little is still known of these mechanisms, thus we focused on MRI abnormalities observable in the tumor and the brain adjacent to the lesion, up to the contralateral hemisphere, with a special interest on tensor diffusion imaging informing on white matter architecture; (2) Material and Methods: volumes, macroscopic volume (MV), brain-adjacent-tumor (BAT) volume and abnormal color-coded DTI volume (aCCV), and region-of-interest samples (probe volumes, ipsi, and contra lateral to the lesion), with their MRI characteristics, apparent diffusion coefficient (ADC), fractional anisotropy (FA) values, and number of fibers (DTI fiber tracking) were analyzed in patients suffering GBM (n = 15) and metastasis (n = 9), and healthy subjects (n = 15), using ad hoc statistical methods (type I error = 5%) (3) Results: GBM volumes were larger than metastasis volumes, aCCV being larger in GBM and BAT ADC was higher in metastasis, ADC decreased centripetally in metastasis, FA increased centripetally either in GBM or metastasis, MV and BAT FA values were higher in GBM, ipsi FA values of GBM ROIs were higher than those of metastasis, and the GBM ipsi number of fibers was higher than the GBM contra number of fibers; (4) Conclusions: The MV, BAT and especially the aCCV, as well as their related water diffusion characteristics, could be useful biomarkers in oncology and functional oncology.

Detection of the alternative lengthening of telomeres pathway in malignant gliomas for improved molecular diagnosis.

Human malignant gliomas exhibit acquisition of either one of two telomere maintenance mechanisms, resulting from either reactivation of telomerase expression or activation of an alternative lengthening of telomeres (ALT) mechanism. In the present study, we analyzed 63 human malignant gliomas for the presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles) and measured telomerase expression, telomeric DNA content (Telo/Alu method), and telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular markers routinely used in clinical practice. The presence of C-circles significantly correlated with IDH1/2 mutation, MGMT exon 1 methylation, low Ki-67 immunostaining, increased telomeric DNA content, absence of functional ATRX protein and level of HTERT gene expression. In multivariate analysis, we observed a trend to a correlation between elevated TERRA levels and increased survival. Interestingly, the C-circles assay allowed to detect ALT activation in glioblastomas exhibiting wild-type IDH1/2 and ATRX expression. These results suggest that, after the correlations uncovered here have been confirmed on larger numbers of tumors, telomeric markers might be useful in improving diagnosis. They also point out to the utility of using the specific, sensitive and quantitative C-circle and Telo/Alu assays that can work with as few as 30 ng of tumor DNA.