Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays.
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.
Schaefer
Karl-Ludwig
KL
Gerhard-Domagk-Institute of Pathology, University of Münster, Domagkstrasse 17, 48149 Münster, Germany.
Wai
Daniel H
DH
Poremba
Christopher
C
Korsching
Eberhard
E
van Valen
Frans
F
Ozaki
Toshifumi
T
Boecker
Werner
W
Dockhorn-Dworniczak
Barbara
B
D051697:Activating Transcription Factor 1; D000328:Adult; D001859:Bone Neoplasms / Q000737:chemistry / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12; D002892:Chromosomes, Human, Pair 22; D004268:DNA-Binding Proteins; D005260:Female; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000235:genetics; D005360:Fibula; D015870:Gene Expression; D006801:Humans; D008545:Melanoma / Q000737:chemistry / Q000235:genetics*; D009141:Musculoskeletal System; D020890:Neuregulin-1 / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000032:analysis; D012512:Sarcoma, Ewing / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000032:analysis
D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D020890:Neuregulin-1; D015514:Oncogene Proteins, Fusion; D017468:Receptors, Fibroblast Growth Factor; D009418:S100 Proteins; D014157:Transcription Factors; D014746:Vimentin; D005346:Fibroblast Growth Factors; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D020893:Receptor, ErbB-3; D051496:Receptor, Fibroblast Growth Factor, Type 1