SETD2

advertisement

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

1.

2.

3.

4.

5.

6.

7.

8.

9.

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.

Download