Exploring mutations: GNAS and CDC73 in jaw fibroosseous lesions.

Introduction: Benign fibro-osseous lesions have long been an area of diagnostic difficulty due to overlapping of histological and radiological features. Differentiating between these lesions is crucial because of their unique pathogenesis and biological behavior. Ossifying fibroma (OF) and fibrous dysplasia (FD) are the most prevalent lesions. However, not all FD or OF exhibit the typical radiological and histopathological features. In such situations, molecular-level investigations could be essential for precise identification and differentiation.

Aim: To evaluate the screening of GNAS and CDC73 mutations in blood and formalin fixed tumor tissues (FFTT) of FD and OF cases.

Material And Methods: Six blood samples (three cases of FD and JOF each) and thirteen FFTT (six cases of FD and seven cases of JOF) were included in the study. DNA was extracted from peripheral blood samples using salting out method followed by whole exome sequencing. Multiple efforts were made to extract DNA from tumor tissues using various protocols, but no measurable yield was obtained.

Results: DNA derived from blood samples gave successful DNA library preparation and subsequent exome sequencing data generation. We report a pathogenic GNAS mutation (exon8:c.G602A:p.R201H) associated with McCune-Albright syndrome and a novel benign mutation identified in a case of FD (GNAS(NM_000516.7):c.257+687_257+688del) whereas none of the subjects of JOF displayed GNAS and/or CDC73 mutation.

Conclusion: Study observed mutations in GNAS gene in blood samples from FD cases. However, a limitation is that only DNA extracted from blood underwent successful exome sequencing. Potential reason for low-quality DNA extraction from tissue may be attributed to prior fixation procedures conducted on bone specimens.