1. ¹Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
2. ²International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
3. ³Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark
4. ⁴Pathology and Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland

Correspondence: Professor LA Aaltonen, Department of Medical Genetics, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Finland. Tel: +358 9 1911 (direct: +358 9 19125595); Fax: +358 9 19125105; E-mail: lauri.aaltonen@helsinki.fi

Received 6 December 2005; Revised 7 March 2006; Accepted 7 March 2006; Published online 26 April 2006.

Abstract

Germline mutations in the fumarate hydratase (FH) gene were recently shown to predispose to the dominantly inherited syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is characterized by benign leiomyomas of the skin and the uterus, renal cell carcinoma, and uterine leiomyosarcoma. The aim of this study was to identify new families with FH mutations, and to further examine the tumor spectrum associated with FH mutations. FH germline mutations were screened from 89 patients with RCC, skin leiomyomas or ovarian tumors. Subsequently, 13 ovarian and 48 bladder carcinomas were analyzed for somatic FH mutations. Two patients diagnosed with ovarian mucinous cystadenoma (two out of 33, 6%) were found to be FH germline mutation carriers. One of the changes was a novel mutation (Ala231Thr) and the other one (435insAAA) was previously described in FH deficiency families. These results suggest that benign ovarian tumors may be associated with HLRCC.