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Bernd Becker

Publications and source records attributed to Bernd Becker.

21 records · Page 2Linked to original sources

Discrimination between gene expression patterns in the invasive margin and the tumour core of malignant melanomas.

Genes that determine the invasive capacity of the invasive front of malignant melanomas (MM) have not yet been systematically investigated in vivo. Therefore, we combined laser pressure catapulting (LPC) microdissection with cDNA microarray technology (DermArray, Research Genetics, representing about 5700 genes) to systematically analyse differences in gene expression profiles between the invasive margin and the tumour centre in nine cases of vertical growth phase MM. Signal-to-noise statistical algorithms combined with hierarchical clustering were performed to determine class-separating genes. The gene encoding phosphoenolpyruvate carboxykinase 1 (PEPCK), the Homo sapiens gene similar to Saccharomyces cerevisiae SSM4 (TEB4), the gene encoding ribosomal protein L19, the Homo sapiens gene similar to the Aspergillus nidulans SudD (a suppressor of the bimD6 homologue), the gene encoding the interleukin-3 receptor alpha subunit, the gene encoding the inositol 1,4,5-triphosphate 3-kinase isoenzyme, and three anonymous expressed sequence tags were identified as class-separating genes. These genes significantly discriminate between the invasive front and the tumour centre. Using this set of genes, 15 out of 18 LPC-dissected MM regions could be grouped correctly. We conclude that the candidate genes identified could spark further research on MM progression and may provide novel prognostic parameters.

Algorithms↗

Loss of EphB6 expression in metastatic melanoma.

Overexpression of various members of the Eph receptor tyrosine kinases and their ephrin ligands has been frequently reported in cancer. In contrast, a loss of EphB6 gene expression has been correlated with a poor prognosis in human neuroblastoma, suggesting a distinct role for this receptor compared to other family members. More recently, an important role of EphB6 signalling in T-cells has been described, suggesting possibly deleterious immunologic effects of a loss of EphB6 in cancer progression. We investigated the expression of EphB6 in melanocytic tumors. EphB6 mRNA of 22 microdissected tissues (7 benign nevi, 7 melanomas, 8 metastases) and 10 different cell lines (normal melanocytes, non-metastatic/metastatic melanoma cell lines) were measured by quantitative real-time RT-PCR. For visualization of EphB6 protein expression, immunohistochemistry of 32 melanocytic lesions were performed. On the mRNA level, the benign nevi revealed the highest EphB6 expression (mean = 1.43), while melanomas (mean = 0.63) and metastases (mean = 0.08; p=0.001) displayed a progressive and significant reduction of EphB6 expression. Accordingly, established melanoma cell lines with metastatic potential showed low EphB6 expression in comparison to normal melanocytes and to most of the melanoma cell lines. Immunohistochemistry revealed homogeneous staining in common nevi, whereas in malignant melanomas and metastases a heterogeneously positive to completely negative EphB6 staining was observed. Remarkably, Spitz nevi stained similarly to ordinary melanocytic nevi. Taken together, we show that melanoma progression to metastatic disease is associated with a significant reduction of EphB6 gene expression which may have considerable consequences for the prognosis of malignant melanoma patients and possible gene-therapeutic approaches.

Adolescent↗