High frequency of somatic frameshift BHD gene mutations in Birt-Hogg-Dubé-associated renal tumors

J Natl Cancer Inst. 2005 Jun 15;97(12):931-5. doi: 10.1093/jnci/dji154.


The Birt-Hogg-Dubé (BHD) syndrome is an inherited genodermatosis characterized by a predisposition to hamartomatous skin lesions, pulmonary cysts, and renal carcinoma. Seventy-seven renal tumors from 12 patients with germline BHD mutations were examined by DNA sequencing to identify somatic mutations in the second copy of BHD. Sequence alterations were detected in the majority of renal tumors (41 of 77, 53%), with loss of heterozygosity at the BHD locus in a minority of additional tumors (14 of 77, 17%). The somatic mutations were distributed across the entire gene, and the majority resulted in frameshifts that are predicted to truncate the BHD protein. These results support a role for BHD as a tumor suppressor gene that predisposes to the development of renal tumors when both copies are inactivated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Frameshift Mutation*
  • Gene Frequency*
  • Humans
  • Kidney Neoplasms / genetics*
  • Loss of Heterozygosity
  • Proteins / genetics*
  • Proto-Oncogene Proteins
  • Sequence Analysis, DNA
  • Tumor Suppressor Proteins


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