Epigenetics of ALK dependent malignancies

Group Leader:
Gerda Egger

Group Members:
Melanie Hassler
Elisa Redl
Lisa Spaller

Contact:
Clinical Institute of Patholgy
Medical University of Vienna
Währinger Gürtel 18-20
A-1090 Vienna
Phone: +43 1 40400-6389
Email: gerda.egger@meduniwien.ac.at

Funding:
Österreichische Nationalbank

Description:
1- DNA methylation signatures in ALK+ ALCL
2- Biological role of DNMT1 for ALK dependent lymphomagenesis
3- Role of histone deacetylases for ALK+ ALCL
4- Epigenetic therapy

Collaborators:
Suzanne Turner (Cambridge), Lukas Kenner (Vienna)

Publications:
1- Laimer D et al. PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas.
Nat Med. 2012 Nov;18(11):1699-704.
2- Hassler MR, Klisaroska A, Kollmann K, Steiner I, Bilban M, Schiefer AI, Sexl V, Egger G. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine in anaplastic large cell lymphoma.
Biochimie. 2012 Nov;94(11):2297-307.
3- Merkel O et al.
Proc Natl Acad Sci U S A. 2010 Sep 14; 107 (37) :16228-33. PubMed PMID:20805506; PubMed Central PMCID: PMC2941277.
4- Gal-Yam EN, Egger G *, Iniguez L, Holster H, Einarsson S, Zhang X, Lin JC, Liang G, Jones PA, Tanay A. Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line.
Proc Natl Acad Sci U S A. 2008 Sep 2; 105 (35) :12979-84. PubMed PMID:18753622; PubMed Central PMCID: PMC2529074. * equal contribution.
5- Egger G, Jeong S, Escobar SG, Cortez CC, Li TW, Saito Y, Yoo CB, Jones PA, Liang G. Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival.
Proc Natl Acad Sci U S A. 2006 Sep 19; 103 (38) :14080-5. PubMed PMID:16963560; PubMed Central PMCID: PMC1599915.

Weblinks: http://www.meduniwien.ac.at/hp/phd-mst/research-labs/assprofgerda-egger/

Tools:
CD4 NPM-ALK, Dnmt1 fl/fl, Hdac1 fl/fl, Hdac2 fl/fl; ALCL cell lines, FFPE material

Techniques:
Genetic mouse models,
Xenografts,
Chromatin Immunoprecipitation (ChIP), Genome-wide DNA methylation analysis, Bisulfite-based DNA methylation analysis