3084

NRG1

ARIA|GGF|GGF2|HGL|HRG|HRG1|HRGA|MST131|NDF|SMDF;neuregulin 1;NRG1;neuregulin 1

MSTP131|glial growth factor|heregulin, alpha (45kD, ERBB2 p185-activator)|neu differentiation factor|neuregulin 1 type IV beta 1a|neuregulin 1 type IV beta 3|pro-NRG1|pro-neuregulin-1, membrane-bound isoform|sensory and motor neuron derived factor

8p12

protein-coding

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-framefusion 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 tocompare 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 thesegenes are involved in signal transduction pathways that may be critical for maintaining cell transformation; some examples are avian erythroblastic leukemiaviral 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 ourfindings demonstrate the MMSP derivation of GG-62 and may shed light on the mechanisms of tumorigenesis in this rare disease.