Alterations of TGFBR2 and KRAS in cemento-osseous dysplasia of the jaw.

Objective: Cemento-osseous dysplasia (COD) is a common benign fibro-osseous lesion found in the periapical regions of the jaw. Despite its prevalence, the etiopathogenesis of COD remains largely unknown. We conducted targeted sequencing of 1,036 genes on two nondecalcified formalin-fixed, paraffin-embedded COD tissue samples.

Study design: The Promega Maxwell system was used for DNA isolation, while the sequencing method applied was Unmatched Normals and Mutant Allele Status Characterization, a tumor-only variant calling pipeline designed to enhance sensitivity, specificity, and precision in variant detection.

Results: We identified canonical hotspot variants in TGFBR2 (specifically TGFBR2 p.Arg528His and TGFBR2 p.Arg553His) with an allelic frequency (AF) of 3%, and two noncanonical KRAS variants: one splice variant with a 10% AF and one single nucleotide variant (snV), KRAS p.Lys167Arg, with a 1.4% AF in a case. The second case had no gene alterations.

Conclusion: We observed alterations in genes within the RAS-MAPK activation pathway, it is important to note that the allele frequencies were generally low. This suggests that most cells in the sample did not exhibit the variant, indicating that other, yet unidentified genes might be responsible for the pathogenesis. The genes we identified may play a role in the progression at a later stage.