#0163

Concurrent Germline and Somatic Mutations in FLCN and Preliminary Exploration of Its Function

t. wang¹, y. niu¹

¹beijing friendship hospital, urology, beijing, China

Introduction:

Birt–Hogg–Dube syndrome is an autosomal dominant condition that arises from germline folliculin (FLCN) mutations. It is characterized by skin fibrofolliculomas, lung cysts, pneumothorax, and renal cancer.

Material and methods:

We present the case of a 36-year-old woman with asymptomatic, multiple renal tumors and a history of spontaneous pneumothorax.

Results:

Genetic analysis revealed a hotspot FLCN germline mutation, c.1285dupC (p.H429fs), and a novel somatic mutation, c.470delT (p.F157fs). This information and the results of immunohistochemical analysis of the renal tumors indicated features compatible with a tumor suppressor role of FLCN. Two transcription factors, oncogenic TFEB and TFE3, were shown to be regulated by FLCN inactivation, which results in their nuclear localization. We showed that a deficiency in the tumor suppressor FLCN leads to deregulation of the mammalian target of rapamycin signaling (mTOR) pathway. A potential link between FLCN mutation and ciliary length was also examined.