title: Familial cutaneous leiomyomatosis is a two-hit condition associated with renal cell cancer of characteristic histopathology.
abstract: Little has been known about the molecular background of familial multiple cutaneous leiomyomatosis (MCL). We report here a clinical, histopathological, and molecular study of a multiple cutaneous leiomyomatosis kindred with seven affected members. This detailed study revealed strong features of a recently described cancer predisposition syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC). The family was compatible with linkage to the HLRCC locus in 1q. Also, all seven cutaneous leiomyomas derived from the proband and analyzed for loss of heterozygosity displayed loss of the wild-type allele, confirming the association with a susceptibility gene in chromosome 1q. One individual had had renal cell cancer at the age of 35 years. This tumor displayed a rare papillary histopathology, which appears to be characteristic for HLRCC. The derived linkage, loss of heterozygosity, and clinical data suggest that MCL and HLRCC are a single disease with a variable phenotype. The possibility that members of leiomyomatosis families are predisposed to renal cell cancer should be taken into account.
authors.affiliation: Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Kiuru
authors.forename: V
authors.initials: V
authors.lastname: Launonen
authors.forename: M
authors.initials: M
authors.lastname: Hietala
authors.forename: K
authors.initials: K
authors.lastname: Aittomäki
authors.forename: O
authors.initials: O
authors.lastname: Vierimaa
authors.forename: R
authors.initials: R
authors.lastname: Salovaara
authors.forename: J
authors.initials: J
authors.lastname: Arola
authors.forename: E
authors.initials: E
authors.lastname: Pukkala
authors.forename: P
authors.initials: P
authors.lastname: Sistonen
authors.forename: R
authors.initials: R
authors.lastname: Herva
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007679:Kidney Medulla / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D018231:Leiomyomatosis / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D009378:Neoplasms, Multiple Primary; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics*