Mutations In The Succinate Dehydrogenase Subunit B Gene Associated With Familial Renal Cell Cancer

Previous research suggested that germline mutations in succinate dehydrogenase genes were principally associated with the development of pheochromocytoma or paraganglioma, which are tumor syndromes that affect other tissues. Although RCC had been reported occasionally in individuals with a germline SDHB mutation, these individuals had a personal or family history of pheochromocytoma or paraganglioma. Therefore, the association of mutations in succinate dehydrogenase genes with familial RCC in the absence of other tumor syndromes was unknown.

In the current study, Eamonn Maher, M.D., of the University of Birmingham in the UK and colleagues sequenced the genes encoding several of these enzymes in 68 individuals who had either familial RCC or bilateral RCC but who showed no evidence of pheochromocytoma or paraganglioma.

They identified three individuals with germline mutations in SDHB in this population. They conclude that the mutations are associated with an increased risk of inherited RCC.

"Our findings suggest that individuals presenting with features of inherited RCC susceptibility should be screened for germ¬line SDHB mutations because surveillance for SDHB-related tumors can then be offered to mutation-positive patients and relatives," the authors write.

In an accompanying editorial, Charis Eng, M.D., Ph.D., of the Cleveland Clinic in Ohio notes that the new data confirm previous reports of an association between mutations in the SDHB gene and familial RCC. She thinks, however, that it is too early to conclude whether such mutations occur in the absence of tumor syndromes given the relatively young age at which the three patients in Maher's study either died or were lost to follow-up and the later age of onset for pheochromocytoma or paraganglioma.

Nonetheless, the new data have clinical utility, according to Eng. "It is entirely appropriate, at this time, to counsel patients carrying SDHB mutations, espe¬cially those with Arg mutations, that they have a small but finite likelihood of developing RCC," she writes.