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- Skotheim, RI, et al.
(författare)
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Topoisomerase-II alpha is upregulated in malignant peripheral nerve sheath tumors and associated with clinical outcome
- 2003
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 21:24, s. 4586-4591
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To identify target genes of clinical significance for patients with malignant peripheral-nerve sheath tumor (MPNST), an aggressive cancer for which no consensus therapy exists. Materials and Methods: Biopsies and clinical data from 51 patients with MPNST were included in this study. Based on our previous research implicating chromosome arm 17q amplification in MPNST, we performed gene expression analyses of 14 MPNSTs using chromosome 17-specific cDNA microarrays. Copy numbers of selected gene probes and centromere probes were then determined by interphase fluorescence in situ hybridization in 16 MPNSTs. Finally, we generated a tissue microarray containing 79 samples from 44 MPNSTs, on which in situ protein expressions of candidate genes were examined and related to clinical end points. Results: Among several deregulated genes found by cDNA microarray analyses, topoisomerase IIalpha (TOP2A) was the most overexpressed gene in MPNSTs compared with benign neurofibromas. Excess copies of the TOP2A were also seen at the DNA level in 10 of 16 cases, and high expression of the TOP2A protein was seen in 83% of the tumors on the tissue microarray. The TOP2A-expressing tumors were associated with poor cancer-specific survival and presence of metastases. Conclusion: We have identified TOP2A as a target gene in MPNST, using a focused gene expression profiling followed by a DNA copy number evaluation and clinical validation of the encoded protein using a tissue microarray. This study is the first to suggest that TOP2A expression may be a predictive factor for adverse outcome in MPNST. (C) 2003 by American Society of Clinical Oncology.
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| 2. |
- Tuzmen, S, et al.
(författare)
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Characterization of farnesyl diphosphate farnesyl transferase 1 (FDFT1) expression in cancer
- 2019
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Ingår i: Personalized medicine. - : Future Medicine Ltd. - 1744-828X .- 1741-0541. ; 16:1, s. 51-65
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To help characterize the FDFT1 gene and protein expression in cancer. Cholesterol represents an important structural component of lipid rafts. These specializations can be involved in pathways stimulating cell growth, survival and other processes active in cancer. This cellular compartment can be expanded by acquisition of cholesterol from the circulation or by its synthesis in a metabolic pathway regulated by the FDFT1 enzyme. Given the critical role this might play in carcinogenesis and in the behavior of cancers, we have examined the level of this enzyme in various types of human cancer. Our demonstration of elevated levels of FDFT1 mRNA and protein in some tumors relative to surrounding normal tissue identifies this as a possible biomarker for disease development and progression, and as a potential new target for the treatment of cancer.
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