JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
REVIEW
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The genetic basis of kidney cancer: why is tuberous sclerosis complex often overlooked?

Fifty years ago, the Eker rat was identified as the first animal model of hereditary renal adenoma and carcinoma, with histopathology resembling human renal carcinoma. Ten years ago, a mutation in the TSC2 gene was identified in the Eker rat at Fox Chase Cancer Center by Yeung and Knudson, and in Tokyo by Kobayashi and Hino. The literature contains dozens of reports of renal cell carcinoma (RCC) in tuberous sclerosis complex (TSC) patients, including tumors in children as young as five and one report in an infant. Despite these facts, the association between TSC and RCC is under-recognized, and sometimes completely omitted from discussions of inherited renal carcinoma. Here, we will review the clinical association of RCC in TSC, consider the factors that have led to its under-emphasis within the RCC field, address the cellular and biochemical mechanisms that may contribute to RCC in cells with TSC1 or TSC2 mutations, and finally discuss the ways in which the TSC signaling pathways may be linked to sporadic RCC in the general population.

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