Multiple Desmoplastic Melanomas in Birt-Hogg-Dubé Syndrome and a Proposed Signaling Link Between Folliculin, the mTOR Pathway, and Melanoma Susceptibility

Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant disorder characterized by the development of cutaneous and systemic tumors.¹ The BHD gene (OMIM 135150) codes for the protein folliculin, which is expressed in multiple tissues including kidney, lung, and skin.¹ Folliculin is thought to play a role in tumor suppression exerting an inhibitory effect on the growth-promoting mammalian target of rapamycin (mTOR) pathway.² Mutations observed within the BHD gene in BHDS lead to the expression of inactive folliculin, ultimately resulting in mTOR pathway activation.³ Unregulated mTOR activation promotes cell growth and proliferation, as observed in melanoma pathogenesis.^3,4