Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.
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).
Here we report a case of a 14 year-old patient with germline FLCN mutation leading to an early-onset bulky RCC that could not be classified strictly according to existing histological types.
We also undertook FLCN analysis to evaluate whether unrecognized BHD syndrome might be present in 69 patients with apparent nonsyndromic RCC susceptibility.
These findings define FLCN as a player in HIF-dependent longevity signaling and connect organismal aging, stress resistance, and regulation of longevity with the formation of renal cell carcinoma.
A bona fide tumour suppressor activity of FLCN was confirmed by nude mouse xenograft assays of two human RCC cell lines with either diminished or re-expressed FLCN.
Birt-Hogg-Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene.
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.
To explore therapeutic approaches to renal cell carcinoma in patients with Birt-Hogg-Dubé syndrome we investigated the anticancer effects of irradiation on folliculin deficient renal cancer cells.
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).
It is known that mutation of FLCN can predispose Birt-Hogg-Dubé (BHD) patient's to renal cell carcinoma , renal and lung cysts, as well as skin fibrofolliculomas.
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.
Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC) in Birt-Hogg-Dubé syndrome.
To develop therapeutic approaches for renal cell carcinoma (RCC) in BHD syndrome, we adopted a strategy to identify tumor-selective growth inhibition in a RCC cell line with FLCN inactivation.
During the past decade, researchers have identified the von Hippel-Lindau (VHL) gene as an important tumor suppressor in clear cell carcinoma of the kidney.
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.
Subsequent sequence analysis revealed a heterozygous R988C mutation of the MET gene and a VHL deletion in both the primary tumor and the tumor-derived ccRCC cell line.