Inherited susceptibility to uterine leiomyomas and venal cell cancer

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 u terine leiomyomas and two with uterine leiomyosarcoma. Seven individuals ha d a history of cutaneous nodules, two of which were confirmed to be cutaneo us leiomyomatosis. The four kidney cancer cases occurred in young (33- to 4 8-year-old) females and displayed a unique natural history. All these kidne y cancers displayed a distinct papillary histology and presented as unilate ral solitary lesions that had metastasized at the time of diagnosis. Geneti c-marker analysis mapped the predisposition gene to chromosome 1q. Losses o f the normal chromosome 1q were observed in tumors that had occurred in the kindred, including a uterine leiomyoma. Moreover, the observed histologica l features were used as a tool to diagnose a second kindred displaying the phenotype. We have shown that predisposition to uterine leiomyomas and papi llary renal cell cancer can be inherited dominantly through the hereditary leiomyomatosis and renal cell cancer (HLRCC) gene. The HLRCC gene maps to c hromosome 1q and is likely to be a tumor suppressor. Clinical, histopatholo gical, and molecular tools are now available for accurate detection and dia gnosis of this cancer syndrome.