Inherited susceptibility to uterine leiomyomas and renal cell cancer
- Virpi Launonen*,†,
- Outi Vierimaa†,‡,
- Maija Kiuru*,†,
- Jorma Isola§,
- Stina Roth*,
- Eero Pukkala¶,
- Pertti Sistonen‖,
- Riitta Herva**, and
- Lauri A. Aaltonen*,‡‡
- *Department of Medical Genetics, Haartman Institute, University of Helsinki, P. O. Box 21, FIN-00014, Helsinki, Finland; ‡Department of Clinical Genetics, Oulu University Hospital, Kajaanintie 50, FIN-90220, Oulu, Finland; §Institute of Medical Technology, University of Tampere, FIN-33014, Tampere, Finland; ¶Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Finnish Cancer Registry, FIN-00170, Helsinki, Finland; ‖Finnish Red Cross Blood Transfusion Service, Kivihaantie 7, FIN-00310, Helsinki, Finland; and **Department of Pathology, Oulu University Hospital, Kajaanintie 52, FIN-90220, Oulu, Finland
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Communicated by Albert de la Chapelle, Ohio State University, Columbus, OH (received for review December 21, 2000)
Abstract
Herein we report the clinical, histopathological, and molecular features of a cancer syndrome with predisposition to uterine leiomyomas and papillary renal cell carcinoma. The studied kindred included 11 family members with uterine leiomyomas and two with uterine leiomyosarcoma. Seven individuals had a history of cutaneous nodules, two of which were confirmed to be cutaneous leiomyomatosis. The four kidney cancer cases occurred in young (33- to 48-year-old) females and displayed a unique natural history. All these kidney cancers displayed a distinct papillary histology and presented as unilateral solitary lesions that had metastasized at the time of diagnosis. Genetic-marker analysis mapped the predisposition gene to chromosome 1q. Losses of the normal chromosome 1q were observed in tumors that had occurred in the kindred, including a uterine leiomyoma. Moreover, the observed histological features were used as a tool to diagnose a second kindred displaying the phenotype. We have shown that predisposition to uterine leiomyomas and papillary renal cell cancer can be inherited dominantly through the hereditary leiomyomatosis and renal cell cancer (HLRCC) gene. The HLRCC gene maps to chromosome 1q and is likely to be a tumor suppressor. Clinical, histopathological, and molecular tools are now available for accurate detection and diagnosis of this cancer syndrome.
Footnotes
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↵ † V.L., O.V., and M.K. contributed equally to this work.
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↵ ‡‡ To whom reprint requests should be addressed. E-mail: Lauri.Aaltonen{at}Helsinki.Fi.
- Abbreviations:
- VHL,
- von Hippel-Lindau;
- H&E,
- hematoxylin/eosin;
- HMFG,
- human milk fat globule;
- lod,
- logarithm of odds;
- LOH,
- loss of heterozygosity
- Copyright © 2001, The National Academy of Sciences
