Copy number alterations of the polycomb gene BMI1 in gliomas

Abstract

Gliomas are heterogeneous tumours that grow in an uninhibited fashion, and these brain tumour cells share numerous characteristics with neural stem cells. The BMI1 gene encodes a component of the polycomb protein complex regulating epigenetically gene activity via histone modification. It functions for instance during the development of the central nervous system and maturation of neural cells. BMI-1 protein expression is deregulated in several forms of cancer and gene amplification has been identified in mantle cell lymphomas. Since BMI1 is located at chromosome 10p, a region implicated frequently in brain tumourigenesis, we investigated the genetic status and the corresponding expression patterns of BMI1 in a series of 100 low- and high-grade primary and recurrent gliomas. Chromogenic in situ hybridisation (CISH) with probes directed against BMI1 at 10p13 and the centromere of chromosome 10 was used in the analyses. Of all gliomas, 59% demonstrated aberrant copy numbers of BMI1. Deletions of the BMI1 locus were found in most types of tumours, and in a univariate survival analysis these cases had poor prognosis. Increased copy numbers of the BMI1 locus (3-5 copies) were found in all histological types, especially in high-grade astrocytomas. No difference in prognosis between cases with normal copy numbers and cases with increased copy numbers could be observed. This data suggests that BMI1 gene is aberrant at the chromosomal level in a subset of gliomas, and possibly contributes to brain tumour pathogenesis.

Clinicopathological significance of B-cell-specific Moloney murine leukemia virus insertion site 1 expression in gastric carcinoma and its precancerous lesion

“…It has been shown that Bmi-1 is a key regulator of self-renewal in both normal and tumorigenic human solid tumor stem cells, including several types of brain cancer [10] and breast carcinoma [11] . Dovey et al [12] showed that Bmi-1 is over-expressed in numerous epithelial tumors and plays a key role in lung adenocarcinoma, thus providing a clue to lung cancer cell origin and lung tumorigenesis.…”

Prognostic Value of Combined Immunohistochemical Expression of Bmi1 and Ezh2 in Astrocytoma

“…With regard to involvement of BMI1 in tumor progression, several reports have employed by Bruggeman et al [28], who concluded that BMI1 has been implicated in the pathogenesis of brain tumors such as gliomas. In addition Häyry et al [29], explored the genetic status and the correspondent expression patterns of BMI1 in a series of 100 low-and high-grade primary and recurrent gliomas suggesting that BMI1 possibly contributes to brain tumor pathogenesis. [30], concluded that increased expression of EZH2 in normal breast tissue disposes to subsequent development of cancer, also similar results by Zhang et al [24] , and Ahani et al [31].…”

Overexpression and lack of copy number variation in the BMI-1 gene in human glioma

“…There are only a few studies that have analyzed the role of BMI-1 gene alterations in glioma in clinical samples (12,13). A DNA-RNA-protein analysis on the same sample could provide a complete picture in order to establish the mechanism of BMI-1 regulation.…”

“…Previous studies showed BMI-1 gene alterations such as copy number variations (amplifications and deletions), and overexpression of mRNA and protein in different grades of gliomas (12,13,(27)(28)(29). showed that BMI-1 protein was overexpressed in the majority of grade 2-4 gliomas (12).…”

“…In another study, roughly two-thirds of the total tumors exhibited copy number alterations of BMI-1. It was also shown that there was no correlation between BMI-1 copy number variation and protein expression in glioma (13). Abdouh et al (2009) performed quantitative PCR for the gene amplification analysis and they found that there was no gene amplification, but that there was overexpression of BMI-1 in the glioblastoma samples (11).…”