Birt-Hogg-Dubé (BHD) syndrome, a hereditary renal cancer syndrome caused by mutations in the folliculin (FLCN) gene, is characterized by the presence of fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cell carcinoma (RCC).
In a search for potential synthetic-lethal targets for FLCN using a phosphatase siRNA library screening approach, we found that knockdown of SSH2 serine phosphatase (one of the three members of Slingshot family and previously implicated in actin reorganization) specifically induced Caspase3/7 activity in a dose-dependent manner (up to six-fold increase, 10 nM, 72 h) in two human FLCN-deficient cell lines (BHD-origin renal cell carcinoma UOK257 and thyroid carcinoma FTC133) but not in their folliculin expressing isogenic cell lines.
We describe here a 64-year-old man with a novel germline mutation in the FLCN gene who presented with 3 phenotypically distinct renal tumors in the same kidney, which were histologically classified as oncocytoma (1.4 cm), oncocytic papillary carcinoma (0.5 cm), and clear cell renal carcinoma (0.8 cm).
The BHD gene (also known as folliculin or FLCN) is the gene for Birt-Hogg-Dube syndrome, an autosomal-dominant genodermatosis associated with a hereditary form of chromophobe and oncocytic, hybrid RCC.
It is of great interest to know whether RCCs occurring in the dialytic kidneys harbour the same or similar mutations of the von Hippel-Lindau (VHL) gene as conventional dialysis-unrelated clear cell RCCs so often do.
The meta-analysis showed no association between the VHL gene alteration and overall response rate (relative risk = 1.47 [95% CI, 0.81-2.67], P = 0.20) or progression free survival (hazard ratio = 1.02 [95% CI, 0.72-1.44], P = 0.91) in patients with RCC who received VEGF-targeted therapy.