Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays.

Abstract

GG-62 is a cell line previously thought to be derived from an atypical Ewing tumor (ET). Reverse-transcriptase polymerase chain reaction revealed an in-frame fusion between the Ewing sarcoma gene ( EWS) codon 325 and the activating transcription factor 1 gene ( ATF1) codon 65 which permits the production of chimeric EWS-ATF1 oncoproteins. We also identified the genomic breakpoint resulting from a reciprocal t(12;22)(q13;q12), which is the hallmark of malignant melanoma of soft parts (MMSP). We applied Affymetrix human cancer G110 arrays to compare the gene expression patterns of GG-62 and other cell lines derived from small blue round cell tumors of childhood. Hierarchical clustering of 463 differentially expressed genes distinguished GG-62 from the ETs, as well as the neuroblastomas, and revealed a cluster of 36 upregulated genes. Several of these genes are involved in signal transduction pathways that may be critical for maintaining cell transformation; some examples are avian erythroblastic leukemia viral oncogene homolog 3 ( ERBB3), neuregulin 1 ( NRG1), fibroblast growth factor 9 ( FGF9), and fibroblast growth factor receptor-1 ( FGFR1). Furthermore, genes near the chromosome-12q13 breakpoint exhibited increased expression of GG-62 including ERBB3, NR4A1 (nuclear receptor subfamily 4, group A, member 1), cyclin-dependent kinase 2 ( CDK2), and alpha 5 integrin ( ITGA5). Altogether our findings demonstrate the MMSP derivation of GG-62 and may shed light on the mechanisms of tumorigenesis in this rare disease.

• Authors: Karl-Ludwig Schaefer, Daniel H Wai, Christopher Poremba, Eberhard Korsching, Frans van Valen, Toshifumi Ozaki, Werner Boecker, Barbara Dockhorn-Dworniczak
• Journal: Virchows Archiv : an international journal of pathology (Virchows Arch) Vol. 440 Issue 5 Pg. 476-84 (May 2002) ISSN: 0945-6317 [Print] Germany
• PMID: 12021921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Activating Transcription Factor 1
• DNA-Binding Proteins
• FGF9 protein, human
• Fibroblast Growth Factor 9
• Neuregulin-1
• Oncogene Proteins, Fusion
• Receptors, Fibroblast Growth Factor
• S100 Proteins
• Transcription Factors
• Vimentin
• Fibroblast Growth Factors
• FGFR1 protein, human
• Receptor Protein-Tyrosine Kinases
• Receptor, ErbB-3
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• Activating Transcription Factor 1
• Adult
• Bone Neoplasms (chemistry, genetics)
• Chromosomes, Human, Pair 12
• Chromosomes, Human, Pair 22
• DNA-Binding Proteins
• Female
• Fibroblast Growth Factor 9
• Fibroblast Growth Factors (genetics)
• Fibula
• Gene Expression
• Humans
• Melanoma (chemistry, genetics)
• Musculoskeletal System
• Neuregulin-1 (genetics)
• Neuroblastoma (genetics)
• Oligonucleotide Array Sequence Analysis
• Oncogene Proteins, Fusion (genetics)
• Receptor Protein-Tyrosine Kinases (genetics)
• Receptor, ErbB-3 (genetics)
• Receptor, Fibroblast Growth Factor, Type 1
• Receptors, Fibroblast Growth Factor (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• S100 Proteins (analysis)
• Sarcoma, Ewing (genetics)
• Transcription Factors (genetics)
• Translocation, Genetic
• Tumor Cells, Cultured
• Vimentin (analysis)