C89
Germline SDHB mutations and familial renal cell carcinoma
Christoper Ricketts, Emma Woodward, Pip Killick, Mark Morris, Dewi Astuti, Farida Latif, Eamonn Maher
Cancer Research UK Renal Molecular Oncology Group, Department of Medical and Molecular Genetics, University of Birmingham School of Medicine, Birmingham, UK
Familial Renal Cell Carcinoma (RCC) is a heterogeneous disorder most commonly caused by germline mutations in the VHL, MET and FLCN genes or constitutional chromosome 3 translocations. However in many cases the genetic basis is undefined. We investigated whether germline mutations in fumarate hydratase (FH) or succinate dehydrogenase subunit genes (SDHB, SDHC, SDHD) might cause apparently non-syndromic inherited RCC susceptibility. No mutations in FH, SDHC or SDHD were identified but 3/68 (4.4%) probands had a germline SDHB mutation. Patients with a germline SDHB mutation presented with familial RCC (n=1) or bilateral RCC (n=2) and no personal or family history of phaeochromocytoma or head and neck paraganglioma. Mean age at diagnosis of RCC was 37.8 years (range 24-73). These findings (a) demonstrate that patients with suspected inherited RCC should be examined for germline SDHB mutations, (b) suggest that all SDHB mutation carriers should be offered surveillance for RCC and (c) provide a further link between familial RCC and pseudohypoxic signalling.
