Expression of Birt-Hogg-Dubé gene mRNA in normal and neoplastic human tissues

Mod Pathol. 2004 Aug;17(8):998-1011. doi: 10.1038/modpathol.3800152.


Birt-Hogg-Dubé (BHD) syndrome is an inherited autosomal genodermatosis characterized by hamartomas of the hair follicle called fibrofolliculomas and an increased risk for developing spontaneous pneumothorax, lung cysts and renal neoplasia. BHD was localized to chromosome 17p11.2 by linkage analysis in BHD families, and germline insertion/deletion and nonsense mutations in a novel gene were identified which were predicted to prematurely truncate the BHD protein, folliculin. No homology to other human proteins was found although folliculin was conserved across species. As a first step toward understanding the function of BHD in the cell and how BHD mutations can lead to the BHD phenotype, we measured the expression of BHD mRNA in normal and neoplastic human tissues by fluorescent in situ hybridization. BHD mRNA was expressed in a variety of tissues, including the skin and its appendages, the distal nephron of the kidney, stromal cells and type 1 pneumocytes of the lung, acinar cells of the pancreas and parotid gland, and epithelial ducts of the breast and prostate. In the brain, BHD mRNA was expressed in neurons of the cerebrum, and Purkinje cells in the cerebellum. BHD mRNA was also expressed in macrophage and lymphocytes in the tonsils and spleen. Tissues with reduced expression of BHD mRNA included heart, muscle and liver. BHD mRNA was expressed strongly in the proliferating epithelial strands of fibrofolliculomas, the cutaneous lesions characteristic of BHD, but not in renal tumors from BHD patients. These results indicate a wide expression pattern for BHD mRNA in many tissues, including skin, lung and kidney, which are involved in the BHD phenotype, and support a tumor suppressor role for BHD in renal cancer.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain / metabolism
  • Exocrine Glands / metabolism
  • Fibroma / genetics
  • Fibroma / pathology
  • Gene Expression
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Kidney / metabolism
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Lung / metabolism
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Palatine Tonsil / metabolism
  • Pancreas / metabolism
  • Parotid Gland / metabolism
  • Proteins / genetics*
  • Proto-Oncogene Proteins
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Skin / metabolism
  • Spleen / metabolism
  • Tissue Array Analysis / methods
  • Tumor Suppressor Proteins


  • FLCN protein, human
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins