Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma.

Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder predisposing humans to cutaneous and uterine leiomyomas; in 20% of affected families, type 2 papillary renal cell cancers (PRCCII) also occur with aggressive course and poor prognosis. HLRCC results from heterozygous germline mutations in the tumour suppressor fumarate hydratase (FH) gene.

Methods: As part of the French National Cancer Institute (INCa) 'Inherited predispositions to kidney cancer' network, sequence analysis and a functional study of FH were preformed in 56 families with clinically proven or suspected HLRCC and in 23 patients with isolated PRCCII (5 familial and 18 sporadic).