Kidney cancer characteristics and genotype-phenotype-correlations in Birt-Hogg-Dubé syndrome

PLoS One. 2018 Dec 26;13(12):e0209504. doi: 10.1371/journal.pone.0209504. eCollection 2018.

Abstract

Birt-Hogg-Dubé syndrome (BHDS) is a genetic tumor syndrome characterized by lung cysts, pneumothorax, fibrofolliculomas and renal cell cancer. The diagnosis of BHDS is usually considered if kidney cancer occurs before age 50 years, is multifocal and/or bilateral or of the oncocytoma/hybrid oncocytoma-chromophobe type. Using a sample of 50 BHDS families with a total of 178 patients we analyzed how many kidney cancer patients fulfilled one or more of these criteria. Furthermore, we addressed the question if genotype-phenotype-correlations exist that can be used for risk stratification. Renal cell cancer occurred in 34/178 (19.1%) patients, and the reported male bias was not observed. Furthermore, most kidney malignancies occurred after the age of 50 years. Thus, the majority of tumors did not show the typical hallmarks of BHDS. A below-average tumor frequency (17.2%) was observed for the known mutational hotspot c.1285delC/dupC that was the cause of BHDS in 24% of families. Unexpected was the high tumor frequency (66.7%) associated with mutation c.887C>G within a single family, a finding that merits further exploration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Birt-Hogg-Dube Syndrome / genetics*
  • Carcinoma, Renal Cell / epidemiology
  • Carcinoma, Renal Cell / genetics*
  • Female
  • Genetic Association Studies*
  • Humans
  • Kidney Neoplasms / epidemiology
  • Kidney Neoplasms / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Penetrance
  • Proto-Oncogene Proteins / genetics*
  • Risk Assessment
  • Tumor Suppressor Proteins / genetics*

Substances

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

Grants and funding

This study was supported by the Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der Ludwig-Maximilians-Universität München e. V. to MR (no grant number or URL available). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.