Presentation on theme: "Clear Cell Renal Cell Carcinoma and the Novel Tumor Suppressor SETD2."— Presentation transcript:
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 2342-2348, 11 JUN 2009 DOI: 10.1002/ijc.24642 http://onlinelibrary.wiley.com/doi/10.1002/ijc.24642/full#fig1 Volume 125, Issue 10, http://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
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