Folliculin inactivation and cutaneous leiomyosarcoma in Birt-Hogg-Dubé syndrome.

Abstract

Cutaneous leiomyosarcoma (cLMS) is a rare soft tissue sarcoma where the genetic drivers implicated in carcinogenesis are not completely characterized despite extensive genomic profiling. The presentation of cLMS in Birt-Hogg-Dube (BHD) syndrome, which is caused by heterozygous pathogenic variants in FLCN, adds to our mechanistic understanding of the pathogenesis of cLMS and implicates FLCN loss. In this report, we demonstrate loss of heterozygosity (LOH) of FLCN in BHD cLMS, providing novel genetic evidence that a subset of cLMS may be driven by FLCN loss and that cLMS is an infrequent but recurrent element of the BHD phenotype.