Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that structural abnormalities involving the short arm of chromosome 9 are frequently associated with gliomas. The alpha-, beta-, and omega-interferon (IFNA, IFNB1, and IFNW, respectively) and the methylthioadenosine phosphorylase (MTAP) genes have been mapped to the short arm of chromosome 9, band p22. Homozygous deletions of these genes have been reported in many leukemia- and glioma-derived cell lines. In this report, we present a detailed analysis of partial and complete homozygous or hemizygous deletions of DNA sequences on 9p in human cell lines and primary tumor samples of glioma patients. Ten of 15 (67%) glioma-derived cell lines had hemizygous or homozygous deletion of IFN genes or rearrangement of sequences around these genes, while 13 of 35 (37%) primary glioma tumor samples had hemizygous (8 tumors) or homozygous (5 tumors) deletion of the IFN genes. The shortest region of overlap of these deletions maps in the interval between the centromeric end of the IFN gene cluster and the MTAP gene. In the cell lines and primary tumors examined, these gross genomic alterations were seen only in association with high grade or recurrent gliomas. Our observations confirm that loss of DNA sequences on 9p, particularly the IFN genes, occurs at a significant frequency in gliomas, and may represent an important step in the progression of these tumors. These results are consistent with a model of tumorigenesis in which the development or progression of cancer involves the loss or inactivation of a gene or several genes that normally act to suppress tumorigenesis. One such gene may be located on 9p; this gene may be closely linked to the IFN genes. Nevertheless, loss of the IFN genes, when it occurs, may play an additional role in the progression of these tumors.
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PMID:Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas. 156 21

A large proportion of human tumor-derived cell lines and primary tumor cells show methionine-dependent growth. This phenomenon refers to the ability of cells to grow in media containing methionine and the inability of cells to grow in media supplemented with methionine's precursor, homocysteine (Hcy). Methionine can be formed by two different pathways, the recycling pathway and the salvage pathway. To discover the basis for methionine-dependent growth, we have analyzed 12 tumor cell lines and 2 non-tumor-derived cell lines for defects in two key genes in different methionine synthetic pathways. We found little evidence that defects in methionine synthase expression or mutations in the MS gene are correlated with methionine-dependent growth. However, we did find a correlation between methionine-dependent growth and defects in expression of methylthioadenosine phosphorylase (MTAP), a key enzyme in the salvage pathway. Three of the four cell lines lacking detectable MTAP protein were unable to grow in Hcy-containing media, whereas all six of the MTAP-positive cell lines tested showed strong growth. However, when we introduced MTAP cDNA into MTAP-deficient MCF-7 cells, the resulting cell line was still defective in growth on Hcy, although it could now grow on the salvage pathway precursor methylthioadenosine. These findings indicate that salvage pathway defects are not causally related to methionine-dependent growth.
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PMID:Defects in methylthioadenosine phosphorylase are associated with but not responsible for methionine-dependent tumor cell growth. 1103

The methylthioadenosine phosphorylase (mtap) gene is localized on chromosome 9p21, a chromosomal region often affected by deletion in several kinds of malignant tumors. Studies on malignant melanoma have revealed loss of MTAP expression in vitro and in vivo; however, loss of MTAP expression is mainly regulated by promoter hypermethylation. Loss of MTAP was shown to have an effect on tumor invasion and metastasis. In a recent study, MTAP not only had a role as tumor suppressor but was also implicated in lack of therapeutic response of patients with recurrent malignant melanoma. There is evidence that loss of MTAP results in an inhibition of STAT signaling pathways regulated by interferon. This in turn leads to ineffectiveness of interferon therapy. Determination of the MTAP status in the primary tumor could, therefore, potentially lead to a selection of patients who benefit from interferon treatment.
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PMID:A potential predictive marker for response to interferon in malignant melanoma. 1753 37