Clear cell renal cell carcinoma
Daynna Wolff, PhD FACMG
Yajuan Liu, PhD
Rajyasree Emmadi, MD
Banumathy Gowrishankar, PhD
Jane Houldsworth, PhD
Renal Cell Carcinoma
Clear Cell RCC
This tumor type accounts for ~70% of all renal cell carcinoma cases.
Malignant epithelial cells with clear cytoplasm and a compact-alveolar (nested) or acinar growth pattern interspersed with intricate, arborizing vasculature. A variable proportion of cells with granular eosinophilic cytoplasm may be present. Infrequently, clear cell renal cell carcinoma has a distinct tubular pattern and rarely a pseudopapillary architecture is focally present.
<imagemap> Image:TCGA.RCC.png | 1000px default Explore the data interactively!
The image shows the cumulative copy number of 528 RCC samples from the TCGA (reference needed). Click the image for an interactive version of the data.
|3||Loss||3p (3p21, 3p25 and/or 3p13-p14)|
Mutated in >20%
Mutated in 10-20%
Mutated in 5-10%
Mutated in 2-5%
Note that additional rare gene mutations are listed by Randall et al (2014) 
subset of ccRCC have DNA hypermethylation patterns associated with poor patient outcome
Main Pathways Involved
1) Loss of VHL function results in an uncoupling of an oxygen-sensing pathway, which results in stabilization and activation of the HIF transcription factors, leading to overexpression of a number of factors that promote proliferation, cell survival, angiogenesis, and metabolic changes, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF). 2) histone acetyltranferases/components of the SWI/SNF complex; mutations in chromosome 3p chromatin modifiers PBRM1, SETD2 and BAP1 associated with widspread alterations in transcription or methylation MAP kinase pathway phosphoprotein signature PI3K/AKT and mTOR pathways elevated; high expression of several genes representing targets for immunotherapy including PDCD1, CD247, PDCD1LG2, CTLA4, TNFRSF9, TNFRSF4
Deletion of 3p (bands) or LOH for 3p
Loss of 14, loss of 9p, loss of 18q and highly complex genotype are associated with high risk histological features and adverse clinical outcome, also significantly associated with high risk histologic features: loss of 1p, 4p, 9q, 15q, 16q, 17p, 18p, 21q, 22q and gains of 3q, 5p, 7p, 7q, 17q. Losses of 1p, 4p, 4q, 8p, 9p, 9q, 13q, 14q and 18q correlate with higher grade and/or stage of the tumors  and loss of 4, 9p and 14q have been reported as independent prognostic factors for survival in ccRCC.
Metastatic disease: loss of 21q, 22q
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