The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset (original) (raw)

Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

The data discussed in this publication have been deposited in the NCBI Gene Expression Omnibus database under accession number GSE26372.

References

1. Davies, H. et al. Mutations of the BRAF gene in human cancer. Nature 417, 949–954 (2002)
   Article ADS CAS Google Scholar
2. Wan, P. T. et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF . Cell 116, 855–867 (2004)
   Article CAS Google Scholar
3. Pollock, P. M. et al. High frequency of BRAF mutations in nevi. Nature Genet. 33, 19–20 (2003)
   Article CAS Google Scholar
4. Curtin, J. A. et al. Distinct sets of genetic alterations in melanoma. N. Engl. J. Med. 353, 2135–2147 (2005)
   Article CAS Google Scholar
5. Garraway, L. A. et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436, 117–122 (2005)
   Article ADS CAS Google Scholar
6. Lin, W. M. et al. Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Res. 68, 664–673 (2008)
   Article CAS Google Scholar
7. Patton, E. E. et al. BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr. Biol. 15, 249–254 (2005)
   Article CAS Google Scholar
8. Beroukhim, R. et al. The landscape of somatic copy-number alteration across human cancers. Nature 463, 899–905 (2010)
   Article ADS CAS Google Scholar
9. Michaloglou, C. et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720–724 (2005)
   Article ADS CAS Google Scholar
10. Dimri, G. P. et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo . Proc. Natl Acad. Sci. USA 92, 9363–9367 (1995)
    Article ADS CAS Google Scholar
11. Santoriello, C. et al. Expression of H-RASV12 in a zebrafish model of Costello syndrome causes cellular senescence in adult proliferating cells. Dis. Model. Mech. 2, 56–67 (2009)
    Article CAS Google Scholar
12. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005)
    Article ADS CAS Google Scholar
13. Mootha, V. K. et al. PGC-1α responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nature Genet. 34, 267–273 (2003)
    Article ADS CAS Google Scholar
14. Bilodeau, S., Kagey, M. H., Frampton, G. M., Rahl, P. B. & Young, R. A. SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes Dev. 23, 2484–2489 (2009)
    Article CAS Google Scholar
15. Wang, H. et al. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol. Cell 12, 475–487 (2003)
    Article CAS Google Scholar
16. Fritsch, L. et al. A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Mol. Cell 37, 46–56 (2010)
    Article ADS CAS Google Scholar
17. Dalgliesh, G. L. et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463, 360–363 (2010)
    Article ADS CAS Google Scholar
18. van Haaften, G. et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nature Genet. 41, 521–523 (2009)
    Article CAS Google Scholar
19. Kwan, K. M. et al. The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs. Dev. Dyn. 236, 3088–3099 (2007)
    Article CAS Google Scholar
20. Beroukhim, R. et al. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc. Natl Acad. Sci. USA 104, 20007–20012 (2007)
    Article ADS CAS Google Scholar
21. Nisolle, M. et al. Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy. Hum. Reprod. 14, 2844–2850 (1999)
    Article CAS Google Scholar
22. Perner, S. et al. EML4-ALK fusion lung cancer: a rare acquired event. Neoplasia 10, 298–302 (2008)
    Article CAS Google Scholar
23. Sarraf, S. A. & Stancheva, I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol. Cell 15, 595–605 (2004)
    Article CAS Google Scholar

Download references

Acknowledgements

We thank D. Harrington, R. White and Y. Zhou for discussions; C. Lawrence, I. Adatto and L.-K. Zhang for expert fish care; G. Frampton for bioinformatics assistance; and K. Kwan, C.-B. Chien, and J. Boehm for reagents. This work was supported by grants from the Damon Runyon Cancer Research Foundation (C.J.C., DRG-1855-05), the Charles A. King Trust Foundation (C.J.C.), a Young Investigator Award from the American Society of Clinical Oncology (Y.H.), the Canadian Institutes of Health Research (S.B.) and the National Institutes of Health (C.J.C., K99AR056899-02; Y.H., K08DK075432-04; R.A.Y., CA146455, HG002668; and L.I.Z., CA103846 and DK055381).

Author information

Author notes

1. Craig J. Ceol & Yariv Houvras
   Present address: Present addresses: Program in Molecular Medicine, Program in Cell Dynamics, and Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. (C.J.C.); Departments of Surgery and Medicine, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York 10065, USA (Y.H.).,
2. Craig J. Ceol and Yariv Houvras: These authors contributed equally to this work.

Authors and Affiliations

1. Stem Cell Program and Hematology/Oncology, Children’s Hospital Boston, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA
   Craig J. Ceol, Yariv Houvras, Caitlin Bourque, Christopher J. Burke, Laura Turner, Audrey Uong & Leonard I. Zon
2. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, 02114, Massachusetts, USA
   Yariv Houvras
3. Departments of Medical Oncology, Cancer Biology, and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA
   Judit Jane-Valbuena, William M. Lin, Laura A. Johnson, Rameen Beroukhim, Craig H. Mermel & Levi A. Garraway
4. The Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA
   Judit Jane-Valbuena, William M. Lin, Laura A. Johnson, Rameen Beroukhim, Craig H. Mermel & Levi A. Garraway
5. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, 02142, Massachusetts, USA
   Steve Bilodeau, David A. Orlando & Richard A. Young
6. UMR7216 Epigénétique et Destin Cellulaire, CNRS, Université Paris-Diderot, 35 rue Hélène Brion, Paris, 75013, France
   Valentine Battisti, Lauriane Fritsch & Slimane Ait-Si-Ali
7. Center for Molecular Oncologic Pathology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA
   Travis J. Hollmann & Massimo Loda
8. A. Rossi Fanelli Biochemical Sciences Department, Sapienza University of Rome, Rome 00185, Italy
   Fabrizio Ferré

Authors

1. Craig J. Ceol
   You can also search for this author inPubMed Google Scholar
2. Yariv Houvras
   You can also search for this author inPubMed Google Scholar
3. Judit Jane-Valbuena
   You can also search for this author inPubMed Google Scholar
4. Steve Bilodeau
   You can also search for this author inPubMed Google Scholar
5. David A. Orlando
   You can also search for this author inPubMed Google Scholar
6. Valentine Battisti
   You can also search for this author inPubMed Google Scholar
7. Lauriane Fritsch
   You can also search for this author inPubMed Google Scholar
8. William M. Lin
   You can also search for this author inPubMed Google Scholar
9. Travis J. Hollmann
   You can also search for this author inPubMed Google Scholar
10. Fabrizio Ferré
    You can also search for this author inPubMed Google Scholar
11. Caitlin Bourque
    You can also search for this author inPubMed Google Scholar
12. Christopher J. Burke
    You can also search for this author inPubMed Google Scholar
13. Laura Turner
    You can also search for this author inPubMed Google Scholar
14. Audrey Uong
    You can also search for this author inPubMed Google Scholar
15. Laura A. Johnson
    You can also search for this author inPubMed Google Scholar
16. Rameen Beroukhim
    You can also search for this author inPubMed Google Scholar
17. Craig H. Mermel
    You can also search for this author inPubMed Google Scholar
18. Massimo Loda
    You can also search for this author inPubMed Google Scholar
19. Slimane Ait-Si-Ali
    You can also search for this author inPubMed Google Scholar
20. Levi A. Garraway
    You can also search for this author inPubMed Google Scholar
21. Richard A. Young
    You can also search for this author inPubMed Google Scholar
22. Leonard I. Zon
    You can also search for this author inPubMed Google Scholar

Contributions

C.J.C. and Y.H. contributed equally to this work and are listed alphabetically. C.J.C., Y.H. and L.I.Z. conceived the project, designed and analysed the experiments, and wrote the manuscript. C.J.C. and Y.H. performed the zebrafish experiments and contributed to the other experiments. J.J.-V. performed the tissue culture experiments. S.B. performed the ChIP-seq experiments and analysed the data. V.B., L.F., S.A.-S.-A. performed the biochemistry studies on SETDB1. L.A.J. performed the fluorescence in situ hybridization studies. T.J.H. performed the immunohistochemistry experiments. W.M.L., R.B. and C.H.M. analysed the copy number data. D.A.O. analysed the _SETDB1_-overexpression microarray data for WM451Lu cells. F.F. designed a database to manage and analyse tumour incidence data. C.B., C.J.B., L.T. and A.U. provided technical assistance. M.L., L.A.G. and R.A.Y. provided input into the preparation of the manuscript.

Corresponding author

Correspondence toLeonard I. Zon.

Ethics declarations

Competing interests

L.I.Z. is a founder and stockholder of Fate Therapeutics and a scientific adviser for Stemgent.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-18 with legends and 2 additional references. (PDF 14772 kb)

Supplementary Tables

This file contains Supplementary Tables 1-5 (Table 1 pp 1-406, Table 2 pp 407-896, Table 3 pp 897-923, Table 4 pg 924 and Table 5 pp 925-926). (PDF 24070 kb)

PowerPoint slides

Rights and permissions

About this article

Cite this article

Ceol, C., Houvras, Y., Jane-Valbuena, J. et al. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset.Nature 471, 513–517 (2011). https://doi.org/10.1038/nature09806

Download citation

• Received: 05 April 2010
• Accepted: 07 January 2011
• Published: 23 March 2011
• Issue Date: 24 March 2011
• DOI: https://doi.org/10.1038/nature09806