The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset

Nature
Craig J CeolLeonard I Zon

Abstract

The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway. BRAF(V600E) mutations are also present in benign melanocytic naevi, highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes. For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumo...Continue Reading

References

Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Nov 26, 2002·Nature Genetics·Pamela M PollockPaul S Meltzer
Mar 24, 2004·Cell·Paul T C WanUNKNOWN Cancer Genome Project
Aug 5, 2005·Nature·Chrysiis MichaloglouDaniel S Peeper
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 18, 2005·The New England Journal of Medicine·John A CurtinBoris C Bastian
Oct 17, 2007·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Kristen M KwanChi-Bin Chien
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rameen BeroukhimWilliam R Sellers
Feb 5, 2008·Cancer Research·William M LinLevi A Garraway
Mar 6, 2008·Neoplasia : an International Journal for Oncology Research·Sven PernerMark A Rubin
Mar 31, 2009·Nature Genetics·Gijs van HaaftenP Andrew Futreal
Feb 19, 2010·Nature·Rameen BeroukhimMatthew Meyerson
Feb 13, 2013·Clinical and Experimental Dermatology·G W M Millington

❮ Previous
Next ❯

Citations

Oct 10, 2013·Human Genetics·Laia Simó-Riudalbas, Manel Esteller
Nov 28, 2013·Trends in Cell Biology·Julien Ablain, Leonard I Zon
May 15, 2013·Nature·Samir ZaidiRichard P Lifton
Oct 11, 2011·Nature Genetics·Stuart MacgregorNicholas K Hayward
Jul 5, 2013·Nature Reviews. Cancer·Jason W Locasale
Aug 24, 2013·Nature Reviews. Cancer·Richard WhiteLeonard Zon
Dec 6, 2011·Oncogene·E-J GeutjesR Bernards
Sep 20, 2011·Human Molecular Genetics·Christopher I AmosQingyi Wei
Feb 6, 2013·ILAR Journal·Michael L KentJeffrey C Wolf
Jun 8, 2013·ILAR Journal·Shama ViraniLaura S Rozek
May 3, 2012·Genes & Development·Liesbeth C W VredeveldDaniel S Peeper
Oct 25, 2011·Pigment Cell & Melanoma Research·Daniel S Peeper
Jan 18, 2012·Pigment Cell & Melanoma Research·Cristina SantorielloMarina Mione
Jan 18, 2012·Pigment Cell & Melanoma Research·Ken Dutton-Regester, Nicholas K Hayward
Jul 4, 2012·The Journal of Clinical Investigation·Cristina Santoriello, Leonard I Zon
Nov 24, 2011·Disease Models & Mechanisms·Vinita A Hajeri, James F Amatruda
Jun 14, 2012·PloS One·Manfred SchartlSvenja Meierjohann
Sep 12, 2013·PloS One·James KozubekSoheil S Dadras
Jun 3, 2011·Endocrine-related Cancer·Caitlin Bourque, Yariv Houvras
Dec 1, 2011·Epigenomics·Inge VerbruggeMichael Bots
Mar 25, 2014·The American Journal of Dermatopathology·Shinpei MiuraTomoyuki Masuda
Jan 28, 2014·Annual Review of Pathology·Boris C Bastian
Mar 30, 2013·Science·Mario L SuvàBradley E Bernstein
Jul 22, 2014·Nature Methods·Qin TangDavid M Langenau
Jul 1, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jonathan J LeeChristine G Lian
Nov 13, 2013·Future Medicinal Chemistry·Bhaskar C DasTodd Evans
Sep 26, 2013·Genome Biology·Abel Gonzalez-PerezNuria Lopez-Bigas
Jan 28, 2016·Biochemistry·Aravind BasavapathruniThomas V Riera

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
xenograft
immunoprecipitation
ChIP-Seq
Assay

Related Concepts

Related Feeds

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.