Genetic alterations associated with adult diffuse astrocytic tumors

Abstract

Astrocytic tumors make up a wide range of neoplasms that differ in their location in the central nervous system, morphologic features, progressive and invasive behaviors, and the age and gender of people they affect. This report reviews the cytogenetic, molecular cytogenetic, and molecular genetic abnormalities associated with diffuse infiltrating astrocytomas in adults. This group of tumors is subdivided into low-grade astrocytomas (WHO grade II), anaplastic astrocytomas (WHO grade III), and glioblastoma multiforme (WHO grade IV).

The cohesin-interacting protein, precocious dissociation of sisters 5A/sister chromatid cohesion protein 112, is up-regulated in human astrocytic tumors

“…U251 cells (5x10 5 ) were transfected with 750 nM Pds5A siRNA as described above and equally distributed to six 60-mm petri-dishes (Corning), filled with 3 ml medium each. The cells were then harvested at 24, 48, 72, 96, 120 and 144 h by trypsinisation and counted using a Fuchs-Rosenthal chamber.…”

“…It is thought that such alterations lead to the deregulation of the signalling network within the cells with the loss of tumor suppressor genes and the overexpression of oncogenes that drive tumorigenesis (3)(4)(5)(6)(7). Usually, the mitotic spindle checkpoint ensures the fidelity of sister chromatid segregation during mitosis by delaying the onset of anaphase until the kinetochores of all the chromosomes have attached to the spindle microtubules (8,9).…”

“…Currently, there are no data concerning Pds5A expression in human astrocytic tumors that display a high level of aneuploidy during their early stages of development (5,44,45). Diffuse astrocytomas WHO grade II (low grade astrocytomas, LGAs) are well differentiated tumors with diffuse infiltration of the adjacent brain parenchyma (46).…”

Identification of novel genomic markers related to progression to glioblastoma through genomic profiling of 25 primary glioma cell lines

“…For this purpose, over the last decade molecular approaches including mutation screening, comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analyses have led to the identification of the most frequently recurring genomic imbalances correlating to each WHO subtype (Koschny et al, 2002;Shapiro, 2002;Kitange et al, 2003) and to the identification of several genes acting in pathways involved in glioma development, either in the initiation stages (p53 and Ras by PDGF-NF1) or in malignant progression (Rb-CDKN2-CDK4) (Zhu and Parada, 2002;Collins, 2004). Deletion of 19q is of particular interest, as it is shared by all three glioma subtypes, occurring in approximately 75% of oligodendroglioma, 45% of mixed OA and 40% of astrocytoma (von Deimling et al, 1992(von Deimling et al, , 1994, where it is associated with the transition from low-grade to anaplasic tumors (Ohgaki et al, 1995;Ritland et al, 1995;Smith et al, 1999).…”

Role of the Centrosomal MARK4 Protein in Gliomagenesis

“…Over the last decade, molecular approaches including mutation screening, LOH and aCGH analyses have led to identify the most frequently recurring genomic imbalances associated with each WHO glioma subtype (Kitange et al, 2005;Koschny et al, 2002;Shapiro, 2002) and hence the driver genes acting in pathways involved in glioma development, either in the initiation stages (Tp53 and Ras by PDGF-NF1) or in malignant progression (Rb-CDKN2-CDK4) (Collins, 2004;Zhu & Parada, 2002). Comprehensive genomic characterization by integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in >200 glioblastomas has then refined the definition of human glioblastoma genes and core pathways (The Cancer Genome Atlas [TGCA] Research Network, 2008).…”