Most patients with the disease are known to carry heterozygous germ line mutations in the fumarate hydratase (FH) gene and can be complicated by tumors in internal organs, especially uterine leiomyoma and renal cell cancer in high frequency.
Heterozygous gene mutations in fumarate hydratase can result in a syndrome characterized by hereditary (cutaneous and uterine) leiomyomatosis and renal cell cancer.
Succinate dehydrogenase and fumarate hydratase are mitochondrial proteins of the TCA cycle and the respiratory chain and when mutated lead to tumours of the nervous system known as paragangliomas and pheochromocytomas, and in the case of fumarate hydratase, cutaneous and uterine leiomyomas and renal cell cancer.
However, investigation of the Mendelian single-gene syndromes, like von Hippel Lindau (VHL: VHL gene), hereditary papillary renal carcinoma (HPRC: c-Met gene), Birt-Hogg-Dubé (BHD: BHD gene), and hereditary leiomyomatosis renal cell cancer (HLRCC: fumarate hydratase gene) provides an opportunity to develop pathway specific therapies.
Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer.
In some families renal cell cancer also forms a component of the complex and as such has been described as hereditary leiomyomatosis and renal cell cancer (HLRCC: OMIM 605839).
Germline mutations in FH predispose individuals to leiomyomas and renal cell cancer (HLRCC), whereas mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL).
Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome.
Loss of function mutations in the fumarate hydratase (fumarase, FH) gene were recently identified as the cause for dominantly inherited uterine and cutaneous leiomyomas and renal cell cancer.
Summarizing these results, it seems unlikely that p53 gene alterations will serve as an important new factor for the clinical prognosis of patients with renal-cell cancer.
Pediatric renal cell carcinoma (RCC) associated with ASPL-TFE3 gene fusion resulting from balanced translocation, t(X;17)(p11.2;q25), is a distinctive tumor entity.
Thus, immunotherapy with high-dose bolus IL-2 should be considered as initial therapy for appropriately selected patients with metastatic melanoma and renal cell cancer.