Clear Cell Renal Cell Carcinoma and the Novel Tumor Suppressor SETD2

Histological subtypes of RCC show unique chromosomal abnormalities

Clear Cell RCC nodular growth with areas of hemorrhage and necrosis

3p deletions

Papillary RCC solid white mass

Trisomy 7 and 17, loss of Y

Chromophobe RCC

expansile mass with a solid yellow-brown cut surface

Loss of multiple chromosomes

1, 2, 6, 10,

ccRCC lines show lack of solid tumor hallmarks such as RAS, BRAF, TP53, PTEN and EGFR

Inactivation of the VHL is not sufficient to cause ccRCC in mice

ccRCC is characterized by LOH of chromosome 3

International Journal of CancerVolume 125, Issue 10, pages 2342-2348, 11 JUN 2009 DOI: 10.1002/ijc.24642http://onlinelibrary.wiley.com/doi/10.1002/ijc.24642/full#fig1

Histones organize DNA, regulate expression, and can be modified

During transcription, histones are transiently both modified and exchanged

SETD2 is a non-redundant H3K36-specific trimethyltransferase

SETD2 regulates cryptic transcription at internal exons

SETD2 is necessary for chromatin-remodeler FACT’s recruitment

Knockdown of SETD2 decreases H2B occupancy in internal exons

Loss of SETD2 affects vascular remodeling in mice

Changes in SETD2 alter global gene expression

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