BRAF mutation as a novel driver of eosinophilic cystitis

摘要

Eosinophilic cystitis is a rare manifestation of hypereosinophilia and a cause of morbidity, including dysuria and hematuria. Although some cases can be attributed to infection or allergy, most cases are assessed to be idiopathic and treated with corticosteroids. However, hypereosinophilia can also be due to actionable clonal molecular alterations in the haematopoietic cells, similar to other myeloproliferative neoplasms. Common mutations associated with eosonophilic syndromes are of platelet-derived growth factor receptor alpha or beta or c-kit, though other pathogenic mutations have been found by next generation sequencing. Determination of a specific mutation may therefore identify clonality and refine treatment of some cases. Here we review the molecular features of eosinophilic disorders. We also describe the use of a liquid biopsy of circulating cell-free DNA in the workup of a case of eosinophilic cystitis in which next generation sequencing of cell-free DNA showed a BRAF I463T mutation. In silico modeling supports the functional impact and potential clinical relevance of BRAF I463T.