title: Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.
abstract: BACKGROUND
  Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the autosomal dominant heritable syndrome with predisposition to development of renal cell carcinoma and smooth muscle tumours of the skin and uterus.
  
  
  OBJECTIVE
  To measure the fumarate hydratase (FH) enzyme activity in lymphoblastoid cell lines and fibroblast cell lines of individuals with HLRCC and other familial renal cancer syndromes.
  
  
  METHODS
  FH enzyme activity was determined in the whole cell, cytosolic, and mitochondrial fractions in 50 lymphoblastoid and 16 fibroblast cell lines including cell lines from individuals with HLRCC with 16 different mutations.
  
  
  RESULTS
  Lymphoblastoid cell lines (n = 20) and fibroblast cell lines (n = 11) from individuals with HLRCC had lower FH enzyme activity than cells from normal controls (p<0.05). The enzyme activity in lymphoblastoid cell lines from three individuals with mutations in R190 was not significantly different from individuals with other missense mutations. The cytosolic and mitochondrial FH activity of cell lines from individuals with HLRCC was reduced compared with those from control cell lines (p<0.05). There was no significant difference in enzyme activity between control cell lines (n = 4) and cell lines from affected individuals with other hereditary renal cancer syndromes (n = 22).
  
  
  CONCLUSIONS
  FH enzyme activity testing provides a useful diagnostic method for confirmation of clinical diagnosis and screening of at-risk family members.
authors.forename: M
authors.initials: M
authors.lastname: Pithukpakorn
authors.forename: M-H
authors.initials: MH
authors.lastname: Wei
authors.forename: O
authors.initials: O
authors.lastname: Toure
authors.forename: P J
authors.initials: PJ
authors.lastname: Steinbach
authors.forename: G M
authors.initials: GM
authors.lastname: Glenn
authors.forename: B
authors.initials: B
authors.lastname: Zbar
authors.forename: W M
authors.initials: WM
authors.lastname: Linehan
authors.forename: J R
authors.initials: JR
authors.lastname: Toro
mesh_terms: D000595:Amino Acid Sequence; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology*; D005649:Fumarate Hydratase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018231:Leiomyomatosis / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000201:enzymology*; D010375:Pedigree; D010641:Phenotype; D017386:Sequence Homology, Amino Acid
chemical_list: D005649:Fumarate Hydratase