Identification of new genes associated with melanoma.

Abstract

PURPOSE:

Repeated failures in melanoma therapy made clear that the molecular mechanisms leading to melanoma are still poorly understood. In this study, we aim to provide a more comprehensive understanding of the transcriptional profiles and signalling pathways associated with melanoma.

METHODS:

Gene expression was analysed using the Affymetrix Human Genome U133A 2.0 GeneChip arrays. To avoid culture artifacts, we used microdissected fresh frozen material of 18 melanocytic nevi (MN), 20 primary melanomas (PM) and 20 metastatic melanomas (MM). Statistical analysis was performed with Genomatix Chipinspector, Ingenuity™ Software, SPSS Software and Partek Genomic Suite 6.4. Expression levels of selected transcripts were verified by quantitative real-time RT-PCR and immunostaining of a tissue microarray sampling more than 280 cases of MN, PM and MM with known clinical outcome.

RESULTS:

A total of 284 differentially expressed genes was detected in PM compared with MN and 189 genes in MM compared with PM affecting common cancer pathways such as MAPK-, Wnt- and Notch-signalling. Using principal component analysis, the samples could be grouped according to their histological entity. We identified a panel of novel melanoma-associated markers: frizzled-related protein, an antagonist of Wnt; tranducin-like enhancer of split 1, a transcription factor partner of TCF/LEF-1; CNTN1, an activator of Notch signalling; two Serpin peptidase inhibitors, Serpin B3/B4 and the TGF-β family member GDF15, the latter with association to MAPK-signalling.

• Authors: Andreas Mauerer, Alexander Roesch, Christian Hafner, Thomas Stempfl, Peter Wild, Stefanie Meyer, Michael Landthaler, Thomas Vogt
• Journal: Experimental dermatology (Exp Dermatol) Vol. 20 Issue 6 Pg. 502-7 (Jun 2011) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 21410771 (Publication Type: Journal Article)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Biomarkers, Tumor
• CNTN1 protein, human
• Contactin 1
• DNA Primers
• GDF15 protein, human
• Growth Differentiation Factor 15
• RNA, Neoplasm
• MMP1 protein, human
• Matrix Metalloproteinase 1

Topics

• Adolescent
• Adult
• Aged
• Base Sequence
• Biomarkers, Tumor (genetics, metabolism)
• Child
• Contactin 1 (genetics, metabolism)
• DNA Primers (genetics)
• Disease Progression
• Female
• Gene Expression Profiling
• Genome-Wide Association Study
• Growth Differentiation Factor 15 (genetics, metabolism)
• Humans
• MAP Kinase Signaling System (genetics)
• Male
• Matrix Metalloproteinase 1 (genetics, metabolism)
• Melanoma (genetics, metabolism, secondary)
• Middle Aged
• Nevus, Pigmented (genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• RNA, Neoplasm (genetics, metabolism)
• Skin Neoplasms (genetics, metabolism)
• Young Adult