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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Clin+Oncol
2014 ; 32
(18
): 1968-76
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Molecular genetics of clear-cell renal cell carcinoma
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Brugarolas J
J Clin Oncol
2014[Jun]; 32
(18
): 1968-76
PMID24821879
show ga
Renal cell carcinoma of clear-cell type (ccRCC) is an enigmatic tumor type,
characterized by frequent inactivation of the VHL gene (infrequently mutated in
other tumor types), responsiveness to angiogenesis inhibitors, and resistance to
both chemotherapy and conventional radiation therapy. ccRCC tumors exhibit
substantial mutation heterogeneity. Recent studies using massively parallel
sequencing technologies have implicated several novel driver genes. In VHL
wild-type tumors, mutations were discovered in TCEB1, which encodes Elongin C, a
protein that binds to VHL and is required for its function. Several additional
tumor suppressor genes have been identified near the VHL gene, within a region
that is frequently deleted in ccRCC on chromosome 3p: SETD2, BAP1, and PBRM1.
Mutations in BAP1 and PBRM1 are largely mutually exclusive and are associated
with different tumor biology and patient outcomes. In addition, the mTORC1
pathway is deregulated by mutations in MTOR, TSC1, PIK3CA, and PTEN in
approximately 20% of ccRCCs. Mutations in TSC1, and possibly other genes, may
predict for sensitivity to mTORC1 inhibitors. These discoveries provide insight
into ccRCC development and set the foundation for the first molecular genetic
classification of the disease, paving the way for subtype-specific therapies.
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