Microarray Gene Expression Profiling in Meningiomas and Schwannomas

Abstract

Microarray gene expression profiling is a high throughput system recently used in basic and applied research. It provides a large amount of data -at molecular level- that once acquired, must be functionally integrated in order to find common patterns within a defined group of biological samples. In addition to identification of differentially expressed genes and the establishment of gene regulation patterns, microarrays may also allow us to discover new tumor markers that could have a great impact on the improvement of clinical practice and therapeutics for cancer. The classification method used for cancer is currently based on the morphological characteristics of the biological samples. The information obtained with this method is limited, omitting many important tumor characteristics like the proliferation rate, the capacity of invasion and metastases, as well as the possible development of mechanisms of cellular resistance to treatment. Microarrays can be used in combination with conventional diagnostics as a helpful complement. In this review we focus on how this technology has contributed to our knowledge of the molecular pathogenesis of meningiomas and schwannomas, its potential role as a useful tool for tumor classification and its application in clinical practice.

Microarray gene expression profiling in meningiomas: Differential expression according to grade or histopathological subtype

“…Microarray transcriptomic studies might be a useful complement to conventional diagnosis (70). Our data on the differential expression of gene transcripts in the three groups of meningiomas remain to be validated immunohistochemically when antibodies are available for proteins such as CKS2, UBE2C, GPX3, AOX1 and SERPINF1.…”

Genomic and Expression Alterations of Tumor Suppressor Genes in Meningioma Development, Progression and Recurrence

“…This gene encodes for the Protein 4.1B, located on chromosome 18p11.3. DAL1 gene is generally expressed at high levels in the brain and low levels in the kidney, intestine and testicles (Martinez-Glez, Franco-Hernandez et al 2008). DAL1 loss, together with reduced protein expression of its gene product was detected in sporadic meningiomas, affecting more than 70% of tumors regardless of histological grade (Gutmann, Donahoe et al 2000;Perry, Cai et al 2000).…”

“…The low mutational frequency of this gene discounts sequence variations in DAL1 as the main mechanism underlying participation of this gene in the neoplastic transformation of meningiomas, and suggests that other inactivating mechanism, such as epigenetic changes, may participate in DAL1 silencing (Martinez-Glez, . Additional analyses have shown that DAL1 suppresses the growth and cellular proliferation in meningiomas by activating, among others, the Rac1-dependent c-Jun-NH(2)-kinase signaling pathway (Martinez-Glez, Franco-Hernandez et al 2008). However, the fact that transgenic mice lacking DAL1 do not develop tumors (Yi, McCarty et al 2005), suggests that DAL1 alterations may represent an early progression associated rather than an initiation event for the development of meningiomas.…”

“…However, the analysis of these alterations in relation to histological grade has led to a model in which genetic aberrations are presumably involved in the formation of meningiomas, with subsequent alterations associated with tumor progression (Lomas, Bello et al 2005;Martinez-Glez, Franco-Hernandez et al 2008). Meningiomas were among the first solid tumors recognized as being characterized by a specific cytogenetic alteration, which is monosomy 22.…”

“…Epigenetic alterations seem also to play an important role in the tumorigenesis of meningiomas, as occurs in many other tumor types. These alterations indicate that the silencing by aberrant hypermethylation of gene promoter regions contributes to the genesis and tumor progression of meningiomas (Martinez-Glez, Franco-Hernandez et al 2008). In these tumors, aberrant promoter hypermethylation of CpG dinucleotides of several TSG has been described, including NF2 (26%), THBS1 (15-30%), TIMP-3 (24%), CDKN2A (10-17%), MGMT (6-16%), p73 (15%), ER (15%), GSTP1 (27%), RB1 (10%), DAPK1 (4%), VHL (4%) and CDKN2B (4-13%) (Bello, Amiñoso et al 2004;Liu, Pang et al 2005).…”