What is the role of genetics in the etiology of clear cell renal cell carcinoma (CCRCC)?

Updated: Mar 11, 2019
  • Author: Ronald J Cohen, MB, BCh, PhD, FRCPA, FFPATH; Chief Editor: Liang Cheng, MD  more...
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The main inherited disorder predisposing to development CCRCC is von Hippel-Lindau (VHL) disease, which involves a germline mutation of the VHL gene at chromosome 3p25. Affected individuals are susceptible to tumors of multiple organ systems, including cysts and tumors of the kidney, which occur in 25-45% of cases with a mean age at onset of 40 years. The renal tumors are frequently multifocal and/or bilateral and are always of the clear cell renal cell carcinoma (CCRCC) histologic type. [13]

Other familial disorders that carry an increased risk for the development of CCRCC include constitutional chromosome 3 translocations, which have been described in 8 families to date. They involve germline translocations between chromosome 3 and chromosomes 1, 2, 4, 6, or 8, which result in loss of genetic material from chromosome 3. [14]

Finally, familial nonsyndromic CCRCC involves families in which multiple relatives develop CCRCCs that often have the hallmarks of hereditary tumors (multifocality, bilaterality, and early age of onset) but for which no genetic cause has yet been discovered. [15] CCRCC may also arise in patients with tuberous sclerosis complex or Birt-Hogg-Dubé syndrome, although these syndromes mainly predispose to renal angiomyolipomas and chromophobe or oncocytic hybrid tumors, respectively. [16, 17]

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