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.
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.
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.
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.
Several molecular pathways are implicated in renal cell carcinoma (RCC) pathogenesis, including von Hippel--Lindau (VHL) gene inactivation leading to vascular endothelial growth factor (VEGF) expression.
This is especially so in phenotypically variable diseases, such as von Hippel-Lindau disease (vHL). vHL is caused by germline mutations in the VHL gene, which predispose to the development of multiple tumors such as central nervous system hemangioblastomas and renal cell carcinoma (RCC).
Additionally, a new similarity-based multi-objective optimization algorithm (SMO) was developed for training the MCMO to predict ccRCC related gene mutations (VHL, PBRM1 and BAP1) using quantitative CT features.
Chromosome 3p may therefore contain two loci for renal cell carcinoma: one gene (or genes) in 3p13-p14 and the VHL gene in 3p25-p26, whose aberration is also associated with other typical manifestations of VHL.
CLEC3B genetic deletion was coupled with the well‑known genetic loss of the von Hippel‑Lindau tumor suppressor, which is a characteristic oncogenic event during ccRCC carcinogenesis.
Association of GSTT1 non-null and NAT1 slow/rapid genotypes with von Hippel-Lindau tumour suppressor gene transversions in sporadic renal cell carcinoma.
Amplification of DNA from selected cell populations was demonstrated by detecting a loss of heterozygosity (LOH) at the von Hippel-Lindau disease (VHL) gene in an atypical renal lesion and a renal cell carcinoma in a kidney of a VHL patient.
We observed VHL sequence mutations in 75% of ccRCC tumors and, in most cases, the same mutations were detected in both tumors and corresponding biopsies.