Somatic genetic alterations of oncogenes and tumor suppressor genes in cholesteatoma.

Background: Cholesteatoma is a proliferative disease that affects the tympanic cavity and temporal bone. Despite many studies and various theories, the etiopathogenesis of cholesteatoma has not been fully elucidated. Features such as invasion, migration, uncontrolled proliferation, and lack of differentiation are observed in both cholesteatoma and neoplasia.

Aims/objectives: The aim of this study is to investigate somatic genetic alterations in known proto-oncogenes and tumor suppressor genes in cholesteatoma.

Material and methods: 60 different known proto-oncogenes and tumor suppressor genes were comparatively analyzed in cholesteatoma and peripheric blood samples from 15 middle ear cholesteatoma patients using next-generation sequencing.

Results: JAK3 c.2164G > A, TP53 c.284delC, and KRAS c.377A > T alterations were observed in cholesteatoma tissue but not in normal tissue. In addition, 12 different germline variants were also identified in 8 patients.

Conclusions and significance: In this study, the presence of changes in cancer-related genes in cholesteatoma was determined and these changes were discussed in terms of possible clinical applications. We hope that the genetic alterations that emerged in this study, will be beneficial in guiding future research in this field.