Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Roesch, A. et al.

Alexander Roesch, Bernd Becker, Stefan Bentink, Rainer Spang, Annegret Vogl, Ilja Hagen, Michael Landthaler, Thomas Vogt,

Ataxia telangiectasia-mutated gene is a possible biomarker for discrimination of infiltrative deep penetrating nevi and metastatic vertical growth phase melanoma.

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.[1]

References

Ataxia telangiectasia-mutated gene is a possible biomarker for discrimination of infiltrative deep penetrating nevi and metastatic vertical growth phase melanoma. Roesch, A., Becker, B., Bentink, S., Spang, R., Vogl, A., Hagen, I., Landthaler, M., Vogt, T. Cancer Epidemiol. Biomarkers Prev. (2007) [Pubmed]

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