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

Virchows Arch. 2002 May;440(5):476-84. doi: 10.1007/s00428-001-0558-9. Epub 2001 Dec 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1
  • Adult
  • Bone Neoplasms / chemistry
  • Bone Neoplasms / 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
  • Melanoma / 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

Substances

  • 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