Roesch, Alexander and Becker, Bernd and Bentink, Stefan and Spang, Rainer and Vogl, Annegret and Hagen, Ilja and Landthaler, Michael and Vogt, Thomas (2007) Ataxia telangiectasia-mutated gene is a possible biomarker for discrimination of infiltrative deep penetrating Nevi and metastatic vertical growth phase melanoma. CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 16 (11). pp. 2486-2490. ISSN 1055-9965,
Full text not available from this repository. (Request a copy)Abstract
The deep penetrating nevus (DPN) is a variant of benign melanocytic nevus with clinical and histologic features mimicking vertical growth phase, nodular malignant melanoma (NMM). Because fatal misdiagnosis such as NMM occurs in 29% to 40% of the DPN, molecular differentiation markers are highly desirable. Beyond the clinical demand for precise diagnosis and diagnosis-adapted, preventive therapeutic strategies, the DPN represents a valuable natural model for melanocytic invasion without metastatic potential that per se deserves further investigations. In the present study, at first, we used a genome-wide, microarray-based approach to systematically prescreen for possible molecular markers differentially expressed between selected cases of typical DPN (n = 4) and metastatic NMM controls (n = 4). Gene expression profiling was done on Affymetrix Human X3P microarrays. Of the 47,000 genes spotted, we identified a list of 227 transcripts, which remained significantly regulated at a false discovery rate of 5%. Subsequently, we verified the expression of a subset of the most interesting transcripts in a larger immunohistochemical series DPN, n = 17; NMM, n = 16). Of these transcripts, three were selected for immunohistochemical confirmation: tissue inhibitor of metalloproteinase-2, tumor protein D52, and ataxia telangiectasia-mutated gene (ATM). Additional criteria for selection from the list of 227 significantly regulated transcripts were grouping into functional Ingenuity networks and a known melanoma- or cancer-relevant function. Following these criteria, we detected a highly significant up-regulation of ATM transcription in NMM, which was also mirrored by ATM protein up-regulation. In contrast to the other markers, ATM particularly might serve as a suitable diagnostic and reliable discriminator of DPN/NMM because ATM immunoreactivity also showed a reliable staining consistency within all samples of both entities.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FALSE DISCOVERY RATE; SPINDLE CELL NEVUS; MALIGNANT-MELANOMAS; DNA-DAMAGE; PROTEIN; IDENTIFICATION; ACTIVATION; PATHWAYS; LESIONS; ATM; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Humangenetik Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Nov 2020 10:05 |
| Last Modified: | 30 Nov 2020 10:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/31951 |
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