SETD2

Report
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 yellowbrown 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
Histones organize DNA, regulate
expression, and can be modified
During transcription, histones are
transiently both modified and
exchanged
SETD2 is a non-redundant H3K36specific trimethyltransferase
SETD2 regulates cryptic transcription
at internal exons
SETD2 is necessary for chromatinremodeler 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
References
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Kleymenova, E. "Susceptibility to Vascular Neoplasms but No Increased Susceptibility to Renal Carcinogenesis in
Vhl Knockout Mice." Carcinogenesis 25.3 (2003): 309-15.
Duns, Gerben, Inge Van Duivenbode, Jan Osinga, Harrie Hollema, Eva Van Den Berg-De Ruiter, Robert M.W.
Hofstra, and Klaas Kok. "Histone Methyltransferase Gene SETD2, a Novel Tumor Suppressor Gene in Clear Cell
Renal Cell Carcinoma."Cancer Genetics and Cytogenetics 203.1 (2010): 45.
Buning, Ruth, Wiepke Koopmans, Heinz Neumann, Jason Chin, and John Van Noort. "Regulation of Nucleosome
Conformational Dynamics by Post-Translational Histone Modifications Studied with Single-Pair
FRET." Biophysical Journal 98.3 (2010): 475a.
Berger, S.L. The complex language of chromatin regulation during transcription. Nature 447, 407–412
Carvalho, Sílvia, et al. "Histone methyltransferase SETD2 coordinates FACT recruitment with nucleosome
dynamics during transcription." Nucleic acids research 41.5 (2013): 2881-2893.
"Pathology of Clear Cell Renal Cell Carcinoma ." Pathology of Clear Cell Renal Cell Carcinoma. N.p., n.d. Web. 17
Apr. 2013.
Hu, M., X.-J. Sun, Y.-L. Zhang, Y. Kuang, C.-Q. Hu, W.-L. Wu, S.-H. Shen, T.-T. Du, H. Li, F. He, H.-S. Xiao, Z.-G.
Wang, T.-X. Liu, H. Lu, Q.-H. Huang, S.-J. Chen, and Z. Chen. "Histone H3 Lysine 36 Methyltransferase
Hypb/Setd2 Is Required for Embryonic Vascular Remodeling." Proceedings of the National Academy of
Sciences 107.7 (2010): 2956-961.
Sun, X.-J. "Identification and Characterization of a Novel Human Histone H3 Lysine 36-specific
Methyltransferase." Journal of Biological Chemistry 280.42 (2005): 35261-5271.
Chen, Meng, et al. "Genome‐wide profiling of chromosomal alterations in renal cell carcinoma using
high‐density single nucleotide polymorphism arrays."International Journal of Cancer 125.10 (2009): 2342-2348.

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