Birt-Hogg-Dubé syndrome, a genodermatosis that increases risk for renal carcinoma.
Over the past decade cancer-causing genes have been identified for the most common histologic types of renal cancer, specifically clear cell, papillary type 1 and papillary type 2. Genes predisposing to the more rare chromophobe renal carcinoma and renal oncocytoma were unknown until the recent discovery of a novel gene, BHD, on chromosome 17p that was found to be mutated in the germline of affected family members with the Birt-Hogg-Dubé (BHD) syndrome. These patients develop the hallmark BHD skin lesions (fibrofolliculomas), lung cysts and spontaneous pneumothorax. Importantly, BHD patients have an increased risk for developing a variety of renal neoplasia, most commonly chromophobe and oncocytic hybrid tumors. This review will describe the phenotypic manifestations of BHD including the histologic features of BHD-associated renal tumors, the identification of this novel renal cancer-predisposing gene, the BHD mutation spectrum found in BHD patients, and will discuss the potential role of BHD as a tumor suppressor gene.
Schmidt
Laura S
LS
Basic Research Program, SAIC Frederick, Inc., Laboratory of Immunobiology, National Cancer Institute-Frederick, Frederick, MD 21702, USA. schmidtl@ncifcrf.gov
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016368:Frameshift Mutation; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D011030:Pneumothorax / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012307:Risk Factors; D025521:Tumor Suppressor Proteins
C476078:FLCN protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins