These data indicate that selective loss of the 10q25.3 region, including the DMBT1 gene, is not an initiating event in the genesis of astrocytoma grade II.
In this work, we have examined the expression level and the methylation status of the 5' upstream region of the adhesion molecule ADAM23 in two brain tumor cell lines (A172 and T98G) as well as in three primary brain tumors (one grade II astrocytoma and two meningiomas) and 15 glioblastoma xenografts.
The lack of large, whole-arm 1p/19q losses (such as those found in oligodendroglial tumors), aberrant p53 expression, and the predominance of astroglial components may indicate a biologic relationship of the GTNI to diffuse astrocytoma.
Coexistence of p53 gene mutations and the locus of heterozygosity was common, at least in astrocytomas grade III and in glioblastomas, and also occurred in astrocytoma grade II areas.
Further fusions and activating mutations in BRAF were identified in 28% of grade II astrocytomas, highlighting the importance of the ERK/MAP kinase pathway in the development of paediatric low-grade gliomas.
However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.
In conclusion, the present study indicates that caveolin-1 is not useful as diagnostic marker to differentiate grade II astrocytomas from oligodendrogliomas.
The observed global checkpoint signaling, in contrast to only focal areas of overabundant p53 (indicative of p53 mutation) in grade II astrocytomas, are consistent with DDR activation being an early event in gliomagenesis, initially limiting cell proliferation (low Ki-67 index) and selecting for mutations of p53 and likely other genes that allow escape (higher Ki-67 index) from the checkpoint and facilitate tumor progression.
The aim of this study was to analyze the methylation status of four critical tumor-associated genes (MGMT, RARbeta, RASSF1A, CDH13), and investigate possible links with inflammatory (interleukin [IL]-6, IL-8) and angiogenic mediators (vascular endothelial growth factor [VEGF], cyclooxygenase [COX]-2) and clinical outcome in 23 glioma samples (6 grade II astrocytomas, 17 grade IV glioblastomas).