Other Tumor Suppressor Genes

Besides the loss of NF-2 tumor suppressor expression in about 50% of sporadic meni-giomas, the expression of another member of the band-4.1 family of proteins was found to be lost in about 60% of these tumors [40]. This novel tumor suppressor gene, DAL-1 (differentially expressed in adenocarcinoma of the lung) from chromosome 18p11.3, appears to be important in the early stages of meningioma tumorigenesis. Recently, a gene from human chromosome 22 that belongs to the glycosyl-transferase gene family has been isolated. Abnormal function of that gene may be involved in meningioma tumorigenesis by altering the composition of gangliosides and other glycosylated molecules.

Because of a higher incidence of menin-giomas in patients with a history of breast cancer, breast cancer genes BRCA1 and BRCA2 were examined for loss of heterozygosity in meningiomas. However, alterations of these tumor suppressor genes were not detected in meningiomas [41]. Similarly, another tumor suppressor gene, PTEN, was initially suspected as a meningioma tumor suppressor gene because of the gene's location on chromosome 10q, the region with allelic loss commonly associated with malignant progression of menin-giomas. The PTEN gene was recently found to be unaltered in meningiomas, and it was therefore ruled out as a meningioma tumor suppressor gene.

Because the loss of p53 tumor suppressor functions is the most common genetic alteration in human cancer, several studies carried out mutational analysis of p53 gene and p53 protein expression levels in meningioma. While the frequency of p53 alterations in meningiomas varies among studies [42], the common finding is that accumulation of p53 protein is associated with meningiomas with a high proliferative potential, i.e. the anaplastic and recurrent tumors [42]. Mutational analysis of tumors with high level of p53 protein expression suggests that overexpressed p53 protein is often not a mutant, but rather a wild-type p53 protein. It was suggested, therefore, that the accumulation of p53 protein and mutations in p53 gene could be used as a potential marker to detect the progression of meningiomas.

Loss of heterozygosity at chromosome 1p, particularly in the 1p36 and 1p34-p32 regions, is frequently detected in meningiomas. Interestingly, the loss of chromosome 1p was shown to be associated with NF-2 gene alterations and more frequent tumor recurrence following surgery. Because of the large size of chromosome 1p, loss of many genes could account for the more aggressive behavior of meningiomas with monosomy of chromosome 1p. Because the tumor suppressor gene p18

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