Clear Cell Renal Cell Carcinoma and the Novel Tumor Suppressor SETD2

Histological subtypes of RCC show unique chromosomal abnormalities Clear Cell RCCnodular growth with areas of hemorrhage and necrosis 3p deletions Papillary RCCsolid 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 Cancer Volume 125, Issue 10, pages , 11 JUN 2009 DOI: /ijc Volume 125, Issue 10,

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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