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

Karl Ludwig Schaefer, Daniel H. Wai, Christopher Poremba, Eberhard Korsching, Frans Van Valen, Toshihumi Ozaki, Werner Boecker, Barbara Dockhorn-Dworniczak

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)476-484
Number of pages9
JournalVirchows Archiv
Volume440
Issue number5
DOIs
Publication statusPublished - 2002
Externally publishedYes

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Clear Cell Sarcoma
Oligonucleotide Array Sequence Analysis
Cell Line
Genes
Ewing's Sarcoma
Activating Transcription Factor 1
Codon
Fibroblast Growth Factor 9
Nuclear Receptor Subfamily 4, Group A, Member 1
Integrin alpha5
Chromosome Breakpoints
Receptor, Fibroblast Growth Factor, Type 1
Cyclin-Dependent Kinase 2
Neuregulin-1
Oncogene Proteins
Rare Diseases
Reverse Transcriptase Polymerase Chain Reaction
Neuroblastoma
Oncogenes
Cluster Analysis

Keywords

  • Expression microarray
  • Malignant melanoma of soft parts

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Schaefer, K. L., Wai, D. H., Poremba, C., Korsching, E., Van Valen, F., Ozaki, T., ... Dockhorn-Dworniczak, B. (2002). Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays. Virchows Archiv, 440(5), 476-484. https://doi.org/10.1007/s00428-001-0558-9

Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays. / Schaefer, Karl Ludwig; Wai, Daniel H.; Poremba, Christopher; Korsching, Eberhard; Van Valen, Frans; Ozaki, Toshihumi; Boecker, Werner; Dockhorn-Dworniczak, Barbara.

In: Virchows Archiv, Vol. 440, No. 5, 2002, p. 476-484.

Research output: Contribution to journalArticle

Schaefer, KL, Wai, DH, Poremba, C, Korsching, E, Van Valen, F, Ozaki, T, Boecker, W & Dockhorn-Dworniczak, B 2002, 'Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays', Virchows Archiv, vol. 440, no. 5, pp. 476-484. https://doi.org/10.1007/s00428-001-0558-9
Schaefer, Karl Ludwig ; Wai, Daniel H. ; Poremba, Christopher ; Korsching, Eberhard ; Van Valen, Frans ; Ozaki, Toshihumi ; Boecker, Werner ; Dockhorn-Dworniczak, Barbara. / Characterization of the malignant melanoma of soft-parts cell line GG-62 by expression analysis using DNA microarrays. In: Virchows Archiv. 2002 ; Vol. 440, No. 5. pp. 476-484.
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