Succinate dehydrogenase kidney cancer: an aggressive example of the Warburg effect in cancer.
OBJECTIVE
Recently, a new renal cell cancer syndrome has been linked to germline mutation of multiple subunits (SDHB/C/D) of the Krebs cycle enzyme, succinate dehydrogenase. We report our experience with the diagnosis, evaluation and treatment of this novel form of hereditary kidney cancer.


METHODS
Patients with suspected hereditary kidney cancer were enrolled on a National Cancer Institute institutional review board approved protocol to study inherited forms of kidney cancer. Individuals from families with germline SDHB, SDHC and SDHD mutations, and kidney cancer underwent comprehensive clinical and genetic evaluation.


RESULTS
A total of 14 patients from 12 SDHB mutation families were evaluated. Patients presented with renal cell cancer at an early age (33 years, range 15 to 62), metastatic kidney cancer developed in 4 and some families had no manifestation other than kidney tumors. An additional family with 6 individuals found to have clear cell renal cell cancer that presented at a young average age (47 years, range 40 to 53) was identified with a germline SDHC mutation (R133X) Metastatic disease developed in 2 of these family members. A patient with a history of carotid body paragangliomas and an aggressive form of kidney cancer was evaluated from a family with a germline SDHD mutation.


CONCLUSIONS
SDH mutation associated renal cell carcinoma can be an aggressive type of kidney cancer, especially in younger individuals. Although detection and management of early tumors is most often associated with a good outcome, based on our initial experience with these patients and our long-term experience with hereditary leiomyomatosis and renal cell carcinoma, we recommend careful surveillance of patients at risk for SDH mutation associated renal cell carcinoma and wide surgical excision of renal tumors.
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Christopher J
CJ
Ricketts
Brian
B
Shuch
Cathy D
CD
Vocke
Adam R
AR
Metwalli
Gennady
G
Bratslavsky
Lindsay
L
Middelton
Youfeng
Y
Yang
Ming-Hui
MH
Wei
Stephen E
SE
Pautler
James
J
Peterson
Catherine A
CA
Stolle
Berton
B
Zbar
Maria J
MJ
Merino
Laura S
LS
Schmidt
Peter A
PA
Pinto
Ramaprasad
R
Srinivasan
Karel
K
Pacak
W Marston
WM
Linehan
D000293:Adolescent; D000328:Adult; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics / Q000601:surgery; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
D013385:Succinate Dehydrogenase