GNAS mutational analysis in differentiating fibrous dysplasia and ossifying fibroma of the jaw

Abstract

Differential diagnosis of fibrous dysplasia and ossifying fibroma may often pose problems for pathologists. The purpose of this study was to evaluate the value of mutational analysis of the GNAS gene in differentiating these two conditions. DNA samples from patients with fibrous dysplasia (n=30) and ossifying fibroma (n=21) were collected to analyze the presence of GNAS mutations at exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. In all, 90% (27/30) of cases with fibrous dysplasia showed missense mutations of codon 201 at exon 8, with a predilection of arginine-to-histidine substitution (p.R201H, 70%) as opposed to arginine-to-cysteine substitution (p.R201C, 30%), whereas no mutation was detected at exon 9. No mutation was found in all 21 cases with ossifying fibroma. In addition, a meta-analysis of previously published reports on GNAS mutations in fibrous dysplasia and ossifying fibroma was performed to substantiate our findings. A total of 24 reports including 307 cases of fibrous dysplasia and 23 cases of ossifying fibroma were reviewed. The overall incidence of GNAS mutations in fibrous dysplasia was 86% (264/307), and the major types of mutations were also R201H (53%) and R201C (45%). No GNAS mutation was detected in all patients with ossifying fibroma. We also reported one case with uncertain diagnosis due to overlapping clinicopathological features of fibrous dysplasia and ossifying fibroma. An R201H mutation was detected in this case, thus confirming a diagnosis of fibrous dysplasia. Taken together, our findings indicate that mutational analysis of GNAS gene is a reliable adjunct to differentiate ossifying fibroma and fibrous dysplasia of the jaws.