The objective of the present study was to determine whether guanine nucleotide-binding protein α stimulating (GNAS) gene expression correlates with pathognomonic signs by analyzing the mutations, methylation status and G-protein α subunit (Gsα) expression of GNAS in Ewing sarcoma (ES). Formalin-fixed paraffin-embedded tissue samples from 77 patients with primary ES were obtained in South Korea, Argentina and Brazil, and were studied via methylation chip assay and direct sequencing of the GNAS gene and immunohistochemical analysis of Gsα. The mutation and methylation statuses of the GNAS gene were examined. Immunohistochemical results were measured with respect to proportion and staining intensity. The results revealed that GNAS genes in ES tumor samples were less methylated compared with normal controls. No mutations were detected at exons 8 or 9 of the GNAS locus complex on chromosome 20q13.3, indicating that the pathogenesis of ES was not associated with GNAS mutation. Gsα expression correlated well with the methylation status of the GNAS gene. Notably, high Gsα expression was detected more frequently in samples from living patients than from decedents, although this was not statistically significant (P=0.055). In conclusion, GNAS mutation is not associated with the pathogenesis of ES tumors. This finding may be used to differentiate ES tumors from metastatic bone lesions with morphological similarity to ES tumors. Analysis of the methylation status of the GNAS gene and immunohistochemical Gsα expression suggests that hypermethylated GNAS (low Gsα expression) in ES may be associated with unfavorable progression with a non-significant trend.
Keywords: Ewing sarcoma; GNAS.